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Many studies have shown that urokinase plasminogen activator (uPA) is causally involved in promoting cancer invasion and metastasis. Thus, monitoring uPA levels could be very useful in cancer diagnosis, identification of initial metastasis, and guiding cancer treatment. Here, the authors developed a novel and scalable uPA sensor based on a graphene-gold nanoparticle platform that uses fluorescence of quantum dots to rapidly (

The following Investment Committee paper focuses on a proposal for a leveraged buyout on Elekta AB, a key player in the global radiotherapy market which sells in more than 120 countries. In fact, this paper develops a set of value creation strategies, with special focus on Buy-and-Build, based on company and market analysis, reflecting those strategies in a detailed operating model. Subsequently, a capital structure is suggested by assessing past buyout transactions in the healthcare sector and by leveraging the bank case. Finally, the exit returns are estimated complying with industry threshold and a range of exit strategies are analyzed.

The following Investment Committee paper focuses on a proposal for a leveraged buyout on Elekta AB, a key player in the global radiotherapy market which sells in more than 120 countries. In fact, this paper develops a set of value creation strategies (with an emphasis on the Buy & Build strategy) through a detailed analysis of the radiotherapy market and of the competitive advantages of the company. Subsequently, a capital structure is suggested by assessing past buyout transactions in the healthcare sector and by leveraging the bank case. Finally, the exit returns are estimated complying with industry threshold and a range of exit strategies are analyzed.

Advances in cancer treatment have led to improved survival but have also increased morbidity and mortality due to direct side-effects of the treatment on cardiovascular function. This document reviews the different steps in cardiovascular monitoring and decision-making before during and after cancer treatment with potential cardiovascular side-effects.

Biosimilars present a necessary and timely opportunity for physicians, patients and healthcare systems. If suitably developed clinically, manufactured to the correct standards and used appropriately, they can positively impact on the financial sustainability of healthcare systems. A critical consideration regarding the introduction of biosimilars into the clinic centres on the required information concerning all the respective procedures. This position paper aims to describe the issues revolving around biosimilars that are relevant to the field of oncology, especially the prescribers. More specifically, we discuss aspects related to definition, forms of biosimilars, labelling, extrapolation, interchangeability, switching, automatic substitution, clinical standards on safety and efficacy, responsibilities among prescribers and pharmacists, potential impact on financial burden in healthcare and the current scenario and future prospects of biosimilars in Europe and the rest of the world.

Taste acuity of adult patients undergoing cancer treatment has been well investigated; however, studies of taste acuity after completion of cancer treatment are limited, particularly in children. This study aimed to assess taste acuity in pediatric cancer patients after treatment completion. Seventy-three patients who had completed cancer treatment (median age, 13 years; range, 7 - 18 years) and had not received any further treatment for at least 6 months were enrolled. Eighty-one healthy children (median age, 10 years; range, 8 - 19 years) served as controls. We determined the thresholds for four tastes (sweet, salty, sour, and bitter) using the filter-paper disc method. There was no significant difference in the thresholds of taste acuity for the four test solutions between the patient and control groups. The duration since treatment completion (

Multiple myeloma (MM) is an incurable cancer caused by malignant transformation of plasma cells. Transforming growth factor-β activated kinase 1 (MAP3K7, TAK1) is a major regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. Both NF-κB and MAPK control expression of genes with vital roles for drug resistance in MM. TAK1 is an attractive drug target as it switches these survival pathways to cell death. Our analysis showed that patients with high MAP3K7 expression in the tumor had shorter overall and progression free survival. The TAK1-inhibitors NG25 and 5Z-7-oxozeaenol (5Z-7) were cytotoxic to MM cell lines and patient cells. NG25 reduced expression of MYC and E2F controlled genes, involved in tumor cell growth, cell cycle progression and drug resilience. TAK1 can be activated by genotoxic stress. NG25 and 5Z-7 induced both synergistic and additive cytotoxicity in combination with the alkylating agent melphalan. Melphalan activated TAK1, NF-κB, and the MAPKs p38 and c-Jun N-terminal kinase (JNK), as well as a transcriptional UV-response. This was blocked by NG25, and instead apoptosis was activated. MM induce elevated bone-degradation resulting in myeloma bone disease (MBD), which is the main cause of disability and morbidity in MM patients. NG25 and 5Z-7 reduced differentiation and viability of human bone degrading osteoclasts, suggesting that TAK1-inhibition can have a double beneficial effect for patients. In sum, TAK1 is a promising drug target for MM treatment.

Heat shock proteins (HSPs) are chaperones with highly conservative primary structure, necessary in the processes of protein folding to the most energetically advantageous conformation and maintaining their stability. HSPs perform a number of important functions in various cellular processes and are capable of modulating pathophysiological conditions at the cellular and systemic levels. An example is the high level of HSP expression in neoplastic tissues, which disrupts the apoptosis of transformed cells and promotes the processes of proliferation, invasion, and metastasis. In addition, an increasing amount of information is appearing about the participation of HSPs in the formation of multidrug resistance. This paper provides a review of the current state of research on the fundamental importance as well as the diagnostic and prognostic role of various classes of HSP in cancer treatment. It presents the prospects for using HSPs as biological markers of disease progression and targets in various cancer treatment strategies. However, the need for additional research is quite high. Only numerous joint efforts of research groups will allow the effective use of HSPs as a tool to combat cancer.

In this month’s editorial, the PLOS Medicine Editors announce an upcoming Special Issue, with Guest Editors Elaine Mardis and Marc Ladanyi, on actionable advances in research on the cancer genome.

Introduction Patients with cancer undergoing active systemic anticancer treatment (chemotherapy, immunotherapy, targeted, or combination therapy) are at greater risk of COVID-19 infection than persons without cancer. In this paper, the authors analyse the spread of the coronavirus among cancer patients undergoing systemic therapy, and the impact of COVID-19 infection on the continuation of cancer treatment and its outcome at one community hospital in a mid-sized city in the south of Poland. Material and methods Nasopharyngeal swab was the only collection method used to obtain specimens for testing via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Only those with positive RT-PCR results were considered as confirmed SARS-CoV-2 cases. We analysed the medical records of patients quarantined in a hospital clinical oncology ward due to confirmed COVID-19 infection in one member of the group. Qualitative measures are presented as the percentage of their occurrence, and these were evaluated with Fisher’s test. Differences were considered significant at p < 0.05. Results Cancer patients had more frequent confirmed COVID-19 infection than other patients (3.7% vs. 1.2%). Among cancer patients COVID-19 infection was significantly more frequent in women than in men, p = 0.005. The fatality rate was 27.3% in cancer patients undergoing active anticancer therapy, compared to 3% in the general Polish population. Neither heparin nor G-CSF use had any influence on COVID-19 infection. Conclusions In this analysis, the only significant negative factor for COVID-19 infection was female sex, RR (95% CI) = 4.5 (1.3–15.8), (p = 0.005), and this was attributable to individual behaviour.

Nicola Low and colleagues announce a call for research papers on sexually transmitted infections, to accompany a Collection on the topic.

Though promising, identifying synergistic combinations from a large pool of candidate drugs remains challenging for cancer treatment. Due to unclear mechanism and limited confirmed cases, only a few computational algorithms are able to predict drug synergy. Yet they normally require the drug-cell treatment results as an essential input, thus exclude the possibility to pre-screen those unexplored drugs without cell treatment profiling. Based on the largest dataset of 33,574 combinational scenarios, we proposed a handy webserver, H-RACS, to overcome the above problems. Being loaded with chemical structures and target information, H-RACS can recommend potential synergistic pairs between candidate drugs on 928 cell lines of 24 prevalent cancer types. A high model performance was achieved with AUC of 0.89 on independent combinational scenarios. On the second independent validation of DREAM dataset, H-RACS obtained precision of 67% among its top 5% ranking list. When being tested on new combinations and new cell lines, H-RACS showed strong extendibility with AUC of 0.84 and 0.81 respectively. As the first online server freely accessible at http://www.badd-cao.net/h-racs, H-RACS may promote the pre-screening of synergistic combinations for new chemical drugs on unexplored cancers.

Aims to investigate the causative factors and clinical applicability of spontaneous regression of malignant tumours without treatment, a really paradoxical phenomenon with many therapeutic potentialities. Analyses past cases to find that the commonest cause is a preceding episode of high fever‐induced thermal fluctuation which produces fluctuation of biochemical/immunological parameters. Using Prigogine‐Glansdorff‐Langevin stability theory and biocybernetic principles, develops the theoretical foundation of a tumour’s self‐control, homeostasis and regression induced by thermal, radiation or oxygenation fluctuations. Derives a threshold condition of perturbations for producing regression. Presents some striking confirmation of such fluctuation‐induced regression in Ewing tumour, Clear cell cancer and Lewis lung carcinoma. Using experimental data on patients, elucidates a novel therapeutic approach of multi‐modal hyper‐fluctuation utilizing radiotherapeutic hyper‐fractionation, temperature and immune‐status.

Background: With the anti-cancer efficacies of cold atmospheric plasma being increasingly recognized in vitro, a demand on creating an effective tool feasible for in vivo animal treatment has emerged. Methods: Through the use of co-axial needles with different calibers in diameter, we designed a novel in situ ejection source of cold atmospheric plasma, namely invivoPen, for animal experiments. It punches just a single pinhole that could considerably ease the complexity of operating with small animals such as mouse. Results: We showed that invivoPen could deliver similar efficacies as plasma activated medium with reduced cost in suppressing cell proliferation and migration as well as potentially boosting the viabilities of mice receiving invivoPen treatment. Blood test, renal and liver functionalities tests all suggest that physical plasma could effectively return tumor-carrying mice to the healthy state without harm to body conditions, and invivoPen slightly outweighs PAM in boosting animal immunity and reducing inflammation. Conclusion: Our study contributes to the community in providing a minimal invasive in situ plasma source, having partly explained the efficacies of cold atmospheric plasma in treating triple negative breast cancers, and proposing the potential synergies between physical plasma and conventional drugs for cancer treatment.

Methyltransferase-like 1 (METTL1) mediated 7-methylguanosine (m7G) is crucial for the regulation of chemoresistance in cancer treatment. However, the role of METTL1 in regulating chemoresistance of colon cancer (CC) cells to cisplatin is still unclear. This study established the cisplatin-resistant CC (CR-CC) cells and found that METTL1 was low-expressed in CR-CC cells compared to their paired cisplatin-sensitive CC (CS-CC) cells. Besides, overexpressed METTL1 enhanced the cytotoxic effects of cisplatin on CR-CC cells. In addition, miR-149-3p was the downstream target of METTL1, which could be positively regulated by METTL1. Further results validated that miR-149-3p was low-expressed in CR-CC cells comparing to the CS-CC cells. In addition, the promoting effects of overexpressed METTL1 on cisplatin induced CR-CC cell death were abrogated by synergistically knocking down miR-149-3p. Furthermore, S100A4/p53 axis was the downstream target of METTL1 and miR-149-3p, and either overexpressed METTL1 or miR-149-3p increased p53 protein levels in CR-CC cells, which were reversed by upregulating S100A4. Similarly, the promoting effects of overexpressed METTL1 on cisplatin-induced CR-CC cell death were abrogated by overexpressing S100A4. Taken together, overexpression of METTL1 sensitized CR-CC cells to cisplatin by modulating miR-149-3p/S100A4/p53 axis.

Objectives: Radiotherapy is a key cancer treatment modality but is poorly understood by doctors. We sought to evaluate radiation oncology (RO) teaching in medical schools within the United Kingdom (UK) and Republic of Ireland (RoI), as well as any impacts on RO teaching delivery from the coronavirus disease 2019 (COVID-19) pandemic. Methods: A bespoke online survey instrument was developed, piloted and distributed to oncology teaching leads at all UK and RoI medical schools. Questions were designed to capture information on the structure, format, content and faculty for RO teaching, as well as both the actual and the predicted short- and long-term impacts of COVID-19. Results: Responses were received from 29/41 (71%) UK and 5/6 (83%) RoI medical schools. Pre-clinical and clinical oncology teaching was delivered over a median of 2 weeks (IQR 1–6), although only 9 (27%) of 34 responding medical schools had a standalone RO module. RO teaching was most commonly delivered in clinics or wards (n = 26 and 25 respectively). Few medical schools provided teaching on the biological basis for radiotherapy (n = 11) or the RO career pathway (n = 8), and few provide teaching delivered by non-medical RO multidisciplinary team members. There was evidence of short- and long-term disruption to RO teaching from COVID-19. Conclusions: RO teaching in the UK and RoI is limited with minimal coverage of relevant theoretical principles and little exposure to radiotherapy departments and their non-medical team members. The COVID-19 pandemic risks exacerbating trainee doctors’ already constrained exposure to radiotherapy. Advances in knowledge: This study provides the first analysis of radiotherapy-related teaching in the UK and RoI, and the first to explore the impact of the COVID-19 pandemic on radiationoncology teaching.

It is widely accepted that cancer patients have unmet psychosocial needs. There are as yet few guidelines on the appropriate role of a counsellor in centres for cancer treatment. In this study the activities of a radiographer counsellor were audited to try to identify the proportion of patients who would benefit from seeing a counsellor, to estimate the cost of such a service, and to obtain indications of how the effects of counselling could be evaluated. The study suggested that 44% of patients attending for routine radiotherapy have abnormally high levels of anxiety and might benefit from counselling. The Hospital Anxiety and Depression Scale (HADS) is proposed as an objective measure of benefit. Costing and resource allocation are discussed.

The Wee1 inhibitor MK1775 (AZD1775) is currently being tested in clinical trials for cancer treatment. Here, we show that the p53 target and CDK inhibitor p21 protects against MK1775-induced DNA damage during S-phase. Cancer and normal cells deficient for p21 (HCT116 p21-/-, RPE p21-/-, and U2OS transfected with p21 siRNA) showed higher induction of the DNA damage marker γH2AX in S-phase in response to MK1775 compared to the respective parental cells. Furthermore, upon MK1775 treatment the levels of phospho-DNA PKcs S2056 and phospho-RPA S4/S8 were higher in the p21 deficient cells, consistent with increased DNA breakage. Cell cycle analysis revealed that these effects were due to an S-phase function of p21, but MK1775-induced S-phase CDK activity was not altered as measured by CDK-dependent phosphorylations. In the p21 deficient cancer cells MK1775-induced cell death was also increased. Moreover, p21 deficiency sensitized to combined treatment of MK1775 and the CHK1-inhibitor AZD6772, and to the combination of MK1775 with ionizing radiation. These results show that p21 protects cancer cells against Wee1 inhibition and suggest that S-phase functions of p21 contribute to mediate such protection. As p21 can be epigenetically downregulated in human cancer, we propose that p21 levels may be considered during future applications of Wee1 inhibitors.

Galunisertib (Gal) is a transforming growth factor (TGF-β) blockade which is being investigated as a potential tumor immunotherapy candidate drug in clinical trials. However, primary or acquired resistance is often found in the recruited cancer patients, which limits its clinical application. Tumor immune microenvironment can be regulated by intestinal microbiota, leading to different therapeutic outcomes. It is hypothesized that manipulation of cancer patients' intestinal microbiome in the early stage of therapy may be a promising strategy to improve the therapeutic efficacy of Gal. Methods: 4T1 and H22 subcutaneous tumor bearing mice were used to evaluate the therapeutic effect. Escherichia coli strain Nissle 1917 (EcN), a widely used probiotic bacteria, was orally delivered to the tumor bearing mice daily along with Gal treatment. Antitumor effect of the combination therapy was evaluated by tumor volume, histological staining of tumor tissues. Furthermore, flow cytometry was performed to analyze the alteration of immune microenvironment in tumor bed after treatment. The suppressing effect of the combination therapy on tumor invasiveness and metastasis was evaluated in both mice and zebrafish xenografts models. Fecal sample 16S rRNA gene sequencing was conducted to analyze changes of intestinal microbial diversity. The effect of intestinal microbiota on tumor suppression after receiving EcN was further tested by fecal transplant. Results: The therapeutic outcomes in tumor growth inhibition and metastasis suppression of Gal were significantly potentiated by EcN, resulting from the strengthened antitumor immunity. EcN was able to relieve the immunosuppressive tumor microenvironment, which was evidenced by enhanced tumor-specific effector T cells infiltration and dendritic cells activation. Intestinal microbiota was modulated by EcN, illustrated by a shift of gut microbiome toward certain beneficial bacteria. Conclusion: These results suggested that Gal combined with EcN might be a novel therapeutic approach with great potential of clinical implications for cancer prevention or treatment.

With the aim of discovering novel IDO1 inhibitors, a combined similarity search and molecular docking approach was employed to the discovery of 32 hit compounds. Testing the screened hit compounds has led to several novel submicromolar inhibitors. Especially for compounds LVS-019 with cyanopyridine scaffold, showed good IDO1 inhibitory activity. To discover more compounds with similar structures to LVS-019, a shape-based model was then generated on the basis of it and the second-round virtual screening was carried out leading to 23 derivatives. Molecular docking studies suggested a possible binding mode of LVS-019, which provides a good starting point for the development of cyanopyridine scaffold compounds as potent IDO1 inhibitor. To improve potency of these hits, we further designed and synthesised another 14 derivatives of LVS-019. Among these compounds, LBJ-10 showed improved potency compared to the hits and displayed comparable potency to the control GDC-0919 analogue. LBJ-10 can serve as ideal leads for further modifications as IDO1 inhibitors for cancer treatment.

Significance: Terahertz (THz) radiation has demonstrated a great potential in biomedical applications over the past three decades, mainly due to its non-invasive and label-free nature. Among all biological specimens, skin tissue is an optimal sample for the application of THz-based methods because it allows for overcoming some intrinsic limitations of the technique, such as a small penetration depth (0.1 to 0.3 mm for the skin, on average). Aim: We summarize the modern research results achieved when THz technology was applied to the skin, considering applications in both imaging/detection and treatment/modulation of the skin constituents. Approach: We perform a review of literature and analyze the recent research achievements in THz applications for skin diagnosis and investigation. Results: The reviewed results demonstrate the possibilities of THz spectroscopy and imaging, both pulsed and continuous, for diagnosis of skin melanoma and non-melanoma cancer, dysplasia, scars, and diabetic condition, mainly based on the analysis of THz optical properties. The possibility of modulating cell activity and treatment of various diseases by THz-wave exposure is shown as well. Conclusions: The rapid development of THz technologies and the obtained research results for skin tissue highlight the potential of THz waves as a research and therapeutic instrument. The perspectives on the use of THz radiation are related to both non-invasive diagnostics and stimulation and control of different processes in a living skin tissue for regeneration and cancer treatment.

It has been shown that the tumor population growth dynamics in a periodically varying environment can drastically differ from the one in a fixed environment. Thus, the environment of a tumor can potentially be manipulated to suppress cancer progression. Diverse evolutionary processes play vital roles in cancer progression and accordingly, understanding the interplay between these processes is essential in optimizing the treatment strategy. Somatic evolution and genetic instability result in intra‐tumor cell heterogeneity. Various models have been developed to analyze the interactions between different types of tumor cells. Here, models of density‐dependent interaction between different types of tumor cells under fast periodical environmental changes are examined. It is illustrated that tumor population densities, which vary on a slow time scale, are affected by fast environmental variations. Finally, the intriguing density‐dependent interactions in metastatic castration‐resistant prostate cancer (mCRPC) in which the different types of tumor cells are defined with respect to the production of and dependence on testosterone are discussed., The models of density‐dependent interaction between different types of tumor cells under fast periodical environmental changes are examined. Non‐linear dynamical effects in the tumor growth process are discovered. These dynamical effects can be manipulated for controlling the tumor growth process. The density‐dependent interactions in metastatic castrate‐resistant prostate cancer are also discussed.

Reactive oxygen species (ROS), a group of oxygen derived radicals and derivatives, can induce cancer cell death via elevated oxidative stress. A spatiotemporal approach with safe and deep‐tissue penetration capabilities to elevate the intracellular ROS level is highly desirable for precise cancer treatment. Here, a mechanical‐thermal induction therapy (MTIT) strategy is developed for a programmable increase of ROS levels in cancer cells via assembly of magnetic nanocubes integrated with alternating magnetic fields. The magneto‐based mechanical and thermal stimuli can disrupt the lysosomes, which sequentially induce the dysfunction of mitochondria. Importantly, intracellular ROS concentrations are responsive to the magneto‐triggers and play a key role for synergistic cancer treatment. In vivo experiments reveal the effectiveness of MTIT for efficient eradication of glioma and breast cancer. By remote control of the force and heat using magnetic nanocubes, MTIT is a promising physical approach to trigger the biochemical responses for precise cancer treatment., A magnetomechanical thermal induction therapy (MTIT) strategy is developed based on a single platform of assembly of magnetic nanocubes coupled with alternating magnetic fields. There is a synergistic effect between mechanical responses and thermal properties, which is highly efficient both in vitro and in vivo. The mechanisms of the synergistic effect are investigated, which can be attributed to the manipulation of biochemical reactive oxygen species (ROS) signal level. This MTIT strategy holds potential for precise treatment of deep‐seated tumors in a spatiotemporal controllability.

Stimuli‐responsive nanomedicines have become a recent research focus as a candidate for cancer treatment because of their effectiveness, sensibility, and minimal invasiveness. In this work, a novel nanosystem is developed based on Cu2− xS@MnS core–shell nanoparticles (CSNPs) in which the Cu2− xS core serves as a photosensitizer to generate hyperthermia and reactive oxygen species (ROS), and the MnS shell is used in H2O2‐responsive O2 production. Cu2 −xS@MnS CSNPs with an independent core and shell ratio are synthesized by a controllable hot‐injection method, resulting in an optimal photothermal (PT) effect with a PT conversion efficiency of up to 47.9%. An enhanced photodynamic (PD) effect also occurs in an H2O2 environment. More significantly, in vivo experiments demonstrate that Cu2 −xS@MnS CSNPs can mediate tumor shrinkage in both HeLa tumor cell line‐derived xenograft (CDX) and head and neck squamous cell carcinoma (HNSCC) patient‐derived xenograft (PDX) models, with the capability of being used as a T1‐enhanced magnetic resonance (MR) contrast agent. These results suggest the great potential of as‐prepared Cu2 −xS@MnS CSNPs as photo/H2O2‐responsive therapeutic‐agents against tumors, even in a complicated and heterogeneous environment, thus promoting the clinical translation of nanomedicine., Cu2−xS@MnS core–shell nanoparticles are developed for cancer theranostics. The Cu2 −xS core serves as a photosensitizer to generate hyperthermia and reactive oxygen species, and the MnS shell is used in H2O2‐responsive O2 production, therefore mediating tumor shrinkage in both HeLa tumor cell line‐derived xenograft and head and neck squamous cell carcinoma patient‐derived xenograft models, with the capability of being used as a T1‐enhanced magnetic resonance contrast agent.

It is important that patient-reported outcome (PRO) measures used to assess cancer therapies adequately capture the benefits and risks experienced by patients, particularly when adverse event profiles differ across therapies. This study explores the case for augmenting preference-based utility measures to capture the impact of cancer treatment-related symptoms. Additional cancer treatment-related items could be specific (e.g., rash) or global. While specific items are easier to describe and understand, their use may miss rarer symptoms and those that are currently unknown but will arise from future medical advancements. The appropriate number of additional items, the independence of those items, and their impact on the psychometric properties of the core instrument require consideration. Alternatively, a global item could encompass all potential treatment-related symptoms, of any treatments for any disease. However, such an item may not be well understood by general public respondents in valuation exercises. Further challenges include the decision about whether to generate de novo value sets for the modified instrument or to map to existing tariffs. The fluctuating and transient nature of treatment-related symptoms may be inconsistent with the methods used in conventional valuation exercises. Fluctuating symptoms could be missed by sub-optimal measure administration timing. The addition of items also poses double-counting risks. In summary, the addition of treatment-related symptom items could increase the sensitivity of existing utility measures to capture known and unknown treatment effects in oncology, while retaining the core domains. However, more research is needed to investigate the challenges, particularly regarding valuation.

Two population-based surveys on coronavirus disease-2019 (Covid-19)-like symptoms were conducted by BVA-Doxa on representative samples of the general population from Italy and its largest region, Lombardy, with over 10 million inhabitants and heavily struck by Covid-19, on 27-30 March and 3-7 April, on a total of 2000 individuals - 353 from Lombardy. Overall, 14.2% of Italians - and 19.6% in Lombardy - reported Covid-19-like symptoms. The estimated prevalence was higher in the young, in smokers, and in Lombardy over the period 20 March to 7 April. Although the influenza season was ended by mid-March, at least part of the symptoms may be not Covid-19 related. Even assuming that only half are, at least 7% of Italians and 10% in Lombardy had been affected by Covid-19. To these, asymptomatic or paucisymptomatic cases have to be added. These estimates are at least one or two orders of magnitude larger than official registered cases. This has major implications for cancer prevention, management and treatment.

Background: MicroRNA (miRNA) therapeutics are a promising approach to cancer treatment. However, this method faces considerable challenges to achieve tissue-specific, efficient, and safe delivery of miRNAs in vivo. Methods: Herein, we developed a miRNA delivery system based on the in situ self-assembly of Au-miRNA nanocomplexes (Au-miRNA NCs). Within the cancer microenvironment, we constructed in situ self-assembled Au-miRNA NCs by coincubating gold salt and tumor suppressor mimics, such as let-7a, miRNA-34a, and miRNA-200a. Findings: The in vitro experiments demonstrated that characteristic in situ self-assembled Au-miRNA NCs were present in cancer cells and can be taken up to inhibit the proliferation of cancer cells effectively. Most importantly, as proven in subcutaneous tumor treatment models, Au-miRNA NCs were especially useful for accurate target imaging and tumor suppression, with significantly enhanced antitumor effects for combination therapy. Interpretation: These observations highlight that a new strategy for the in situ biosynthesis of Au-let-7a NCs, Au-miR-34a NCs, and Au-miR-200a NCs is feasible, and this may assist in the delivery of more miRNA to tumor cells for cancer treatment. This work opens up new opportunities for the development of miRNA tumor therapy strategies. Funding: National Natural Science Foundation of China (91753106); Primary Research & Development Plan of Jiangsu Province (BE2019716); National Key Research and Development Program of China (2017YFA0205300). Keywords: Nano-complexes, microRNA delivery, In situ self-assembly, Tumor microenvironment, Cancer treatment

Introduction Our aim was to determine the influence of oral and oropharyngeal (OOP) cancer diagnosis on smoking cessation in patients and/or cohabiting smokers. We also aimed to determine whether OOP cancer patients received smoking-cessation advice and evaluated the factors that were influential in aiding them to quit or decrease smoking. Methods This study was conducted at King Fahad Medical City, Saudi Arabia from March 2015 to May 2017. A pre-validated self-administered questionnaire was administered to OOP cancer patients visiting the Dentistry and Head & Neck Oncology outpatient clinics. Sociodemographics and baseline information were obtained from electronic medical records. Data were collected from 203 patients; 88 were ever-smokers and 115 were never-smokers. Results Among patients who were smoking at the time of the OOP cancer diagnosis, 47.7% continued to smoke after the diagnosis. OOP cancer diagnosis was influential in smoking cessation in ever-smoker patients and their cohabiting smokers. The apparent influence of OOP cancer diagnosis was different between cohabiting smokers of ever-smoker patients (n=21/25; 84%) and those of never-smokers (n=10/21; 47.6%). Former-smokers (n=16/19; 84.2%) were less likely to remember receiving smoking-cessation advice than current-smokers (n=17/39; 43.6%). Pressure from family and friends, adverse impact on cancer prognosis, and adverse impact of cancer treatment were influential factors for smoking cessation. Among treatment modalities, combined chemoradiotherapy had the greatest impact (n=10/21; 47.6%) on smoking cessation among patients who stated that oncology treatment was influential in causing them to quit or decrease smoking. Conclusions A substantial number of patients continued to smoke after the OOP cancer diagnosis; however, diagnosis facilitated smoking cessation in many cases. Current smoking status should be reviewed throughout the OOP cancer patient's disease course, and smoking-cessation assistance should be provided where necessary.

Protein therapeutics is playing an increasingly critical role in treatment of human diseases. However, current vectors are captured by the digestive endo-lysosomal system, which results in an extremely low fraction (60% apoptosis, implying significant antitumor activities. Conclusions: This platform gains cellular entry without entrapment in the endo-lysosomes and enables efficient intracellular protein delivery and resultant profound cancer treatment. This platform, with extremely high drug-loading, is a valuable platform for combined cancer therapy with small-molecule drugs and proteins. More importantly, this work offers a robust and safe approach for protein therapeutics and intracellular delivery of other functional peptides, as well as gene-based therapy.

// Costi Alifrangis 1 , Philip Carter 2 , Biancastella Cereser 2 , Pramodh Chandrasinghe 2, 3 , Lisa Del Bel Belluz 2 , Eric Lim 4 , Nina Moderau 2 , Fotini Poyia 2 , Neha Tabassum 2 , Hua Zhang 5 , Jonathan Krell 2 and Justin Stebbing 2 1 Department of Oncology, University College Hospital, London, UK 2 Department of Surgery and Cancer, Imperial College, London, UK 3 Department of Surgery, University of Kelaniya, Kelaniya, Sri Lanka 4 National Heart and Lung Institute, Imperial College, London, UK 5 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Correspondence to: Philip Carter, email: phil.carter@imperial.ac.uk Keywords: tumor profiling; lung cancer; NSCLC; non-small cell lung cancer; cancer treatment Abbreviations: 5FU: fluorouracil; IHC: immunohistochemistry; NSCLC: non-small cell lung cancer; OS: overall survival Received: July 29, 2017 Accepted: January 01, 2018 Published: February 01, 2018 ABSTRACT In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group’s drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor’s molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not ( P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group ( P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival.

Physically precise external-beam radiotherapy (EBRT) technologies may not translate to the best outcome in individual patients. On the other hand, clinical considerations alone are often insufficient to guide the selection of a specific EBRT approach in patients. We examine the ways in which to compare different EBRT approaches based on physical, biological and clinical considerations, and how they can be enhanced with the addition of biophysical models and machine-learning strategies. The process of selecting an EBRT modality is expected to improve in tandem with knowledge-based treatment planning.

Immunotherapy has brought high hopes for cancer treatment, and attracted tremendous resources from the biopharmaceutical community. Here we analyze cancer immunotherapy-related patents granted by the United States Patent and Trademark Office in the past decade (2006-2016). A total of 2,229 patents were identified in 13 subfields. The growth of patent number in this field has outpaced the background rate, with cytokine-related therapies, immune checkpoint inhibitors, and natural killer cell therapies growing the most rapidly. The top 15 assignees possess 27.6% (616) of the patents. Amgen is the largest patent holder, followed by Novartis, and then by Chugai Seiyaku. The top assignees have focused on different subfields, and collaborated with each other for technology development. Our competitive analysis reveals that Novartis, Chugai Seiyaku, and Abbvie lead in both patent number and average quality of patents. Meanwhile, Immunomedics owns a high-quality though relatively small patent portfolio in single-chain variable fragment technology, which is not the focus of the abovementioned forerunners. Overall, our analysis illustrates an ecosystem where industry giants and smaller-size players each occupies a niche. Selection and succession are expected to continue for years in this young ecosystem.

Targeted drug delivery systems (TDDSs) provide a promising approach to overcome the side effect of traditional chemotherapy by specific tumor targeting and drug release. Hyaluronan (HA), as a selective CD44 targeting group, has been widely used in TDDSs for chemotherapy. However, different molecular weight HAs would demonstrate different binding ability to CD44, which may result in different therapeutic effects. Herein, a silica/hydroxyapatite (MSNs/HAP) hybrid carrier loaded with anticancer drug doxorubicin (DOX) (DOX@MSNs/HAP) is fabricated. HA and oligo HA (oHA) are coated onto the nanoparticles (HA‐DOX@MSNs/HAP, oHA‐DOX@MSNs/HAP), respectively, to investigate their performance in tumor targeting ability. oHA‐DOX@MSNs/HAP shows much higher efficiency cellular uptake and drug release in tumor regions due to more effective CD44 targeting of oHA. Thus, the anticancer effect of oHA‐DOX@MSNs/HAP is significantly enhanced compared to HA‐DOX@MSNs/HAP, as demonstrated in a tumor‐bearing mouse model. This study may enable the rational design of nanodrug systems for future tumor‐targeted chemotherapy.

Background Oncology has been facing increasing outpatient activity associated with higher cancer incidence, better survival rates, and more treatment options. Innovative technological solutions could help deal with this increasing demand. Using digital patient-reported outcome measures (PROMs) to identify patients who need a face-to-face (FTF) appointment is a potential approach. Objective This study aims to assess the feasibility of digital PROM questionnaires to enable remote symptom monitoring for patients undergoing cancer treatment and their ability to highlight the requirement for an FTF appointment. Methods This study was performed at a tertiary oncology center between December 2018 and February 2019. The Common Terminology Criteria for Adverse Events were adapted into patient-friendly language to form the basis of treatment-specific digital questionnaires covering specific cancer drugs and radiotherapy treatments. These treatment-specific digital PROM questionnaires were scored by both patients and their clinicians during FTF appointments. Patients and clinicians did not see each other’s scored PROMs. Agreement between patients and clinicians was assessed using descriptive statistics. Patient and staff feedback was also obtained. Results In total, 90 patients participated in the study across 10 different treatment pathways. By comparing paired patient and clinician responses, the sensitivity of the patient-completed questionnaires in correctly highlighting the need for FTF review was 94% (44/47), and all patients with severe or grade 3+ symptoms were identified (6/6, 100%). Patient-completed PROMs appropriately revealed that 29% (26/90) of the participating patients did not need FTF review based on their symptoms alone. Certain oncological treatment pathways, such as immunotherapy, were found to have a larger proportion of patients with minimal symptoms than others, such as conventional chemotherapy. Patient and staff feedback showed high approval of digital PROMs and their potential for use in remote monitoring. Conclusions Digital PROM questionnaires can feasibly highlight the need for FTF review in oncology clinics for treatment. Their use with specific treatments could safely reduce the requirement for FTF care, and future work should evaluate their application in the remote monitoring of patients.

Background The COVID-19 pandemic has disrupted cancer services globally. New Zealand has pursued an elimination strategy to COVID-19, reducing (but not eliminating) this disruption. Early in the pandemic, our national Cancer Control Agency (Te Aho o Te Kahu) began monitoring and reporting on service access to inform national and regional decision-making. In this manuscript we use high-quality, national-level data to describe changes in cancer registrations, diagnosis and treatment over the course of New Zealand's response to COVID-19. Methods Data were sourced (2018–2020) from national collections, including cancer registrations, inpatient hospitalisations and outpatient events. Cancer registrations, diagnostic testing (gastrointestinal endoscopy), surgery (colorectal, lung and prostate surgeries), medical oncology access (first specialist appointments [FSAs] and intravenous chemotherapy attendances) and radiation oncology access (FSAs and megavoltage attendances) were extracted. Descriptive analyses of count data were performed, stratified by ethnicity (Indigenous Māori, Pacific Island, non-Māori/non-Pacific). Findings Compared to 2018–2019, there was a 40% decline in cancer registrations during New Zealand's national shutdown in March-April 2020, increasing back to pre-shutdown levels over subsequent months. While there was a sharp decline in endoscopies, pre-shutdown volumes were achieved again by August. The impact on cancer surgery and medical oncology has been minimal, but there has been an 8% year-to-date decrease in radiation therapy attendances. With the exception of lung cancer, there is no evidence that existing inequities in service access between ethnic groups have been exacerbated by COVID-19. Interpretation The impact of COVID-19 on cancer care in New Zealand has been largely mitigated. The New Zealand experience may provide other agencies or organisations with a sense of the impact of the COVID-19 pandemic on cancer services within a country that has actively pursued elimination of COVID-19. Funding Data were provided by New Zealand's Ministry of Health, and analyses completed by Te Aho o Te Kahu staff.

// Paola de Andrade Mello 1, 2, * , Shu Bian 2, 3, * , Luiz Eduardo Baggio Savio 2, 4 , Haohai Zhang 2, 5 , Jingping Zhang 6 , Wolfgang Junger 6 , Marcia Rosângela Wink 7 , Guido Lenz 8 , Andreia Buffon 1 , Yan Wu 2, ** and Simon Christopher Robson 2, ** 1 Laboratorio de Analises Bioquimicas e Citologicas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil 2 Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard University, Boston, MA, USA 3 Department of Gastroenterology, Tianjin Union Medical Center, Tianjin, P.R. China 4 Programa de Imunobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil 5 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China 6 Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard University, Boston, MA, USA 7 Laboratorio de Biologia Celular, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil 8 Departamento de Biofisica e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil * Co-first author ** Joint senior authors Correspondence to: Simon Christopher Robson, email: srobson@bidmc.harvard.edu Yan Wu, email: ywu@bidmc.harvard.edu Keywords: purinergic signaling, hyperthermia, membrane fluidity, cancer therapy, colon cancer Received: February 22, 2017 Accepted: May 22, 2017 Published: June 21, 2017 ABSTRACT Extracellular ATP (eATP) accumulation within the tumor microenvironment (TME) has the potential to activate purinergic signaling. The eATP evoked signaling effects bolster antitumor immune responses while exerting direct cytotoxicity on tumor cells and vascular endothelial cells, mediated at least in part through P2X7 receptors. Approaches to augment purinergic signaling in TME e.g. by ectonucleotidase CD39 blockade, and/or boosting P2X7 functional responses, might be used as immunomodulatory therapies in cancer treatment. In this study, we delineated the translatable strategy of hyperthermia to demonstrate impacts on P2X7 responsiveness to eATP. Hyperthermia (40°C) was noted to enhance eATP-mediated cytotoxicity on MCA38 colon cancer cells. Increased membrane fluidity induced by hyperthermia boosted P2X7 functionality, potentiating pore opening and modulating downstream AKT/PRAS40/mTOR signaling events. When combined with cisplatin or mitomycin C, hyperthermia and eATP together markedly potentiate cancer cell death. Our data indicate that clinically tolerable hyperthermia with modulated P2X7-purinergic signaling will boost efficacy of conventional cancer treatments.

Di-peptides derived from the human host defense peptide lactoferricin were previously described to specifically interact with the negatively charged lipid phosphatidylserine exposed by cancer cells. In this study one further derivative, namely R-DIM-P-LF11-334 is shown to exhibit even increased cancer toxicity in vitro and in vivo while non-neoplastic cells are not harmed. In liposomal model systems composed of phosphatidylserine mimicking cancerous and phosphatidylcholine mimicking non-cancerous membranes the specific interaction with the cancer marker PS was confirmed by specific induction of membrane perturbation and permeabilization in presence of the peptide. In vitro studies with cell lines of human malignant melanoma, such as A375, or primary cells of human melanoma metastases to the brain, as MUG Mel1, and non-neoplastic human dermal fibroblasts NHDF revealed high cytotoxic effect of R-DIM-P-LF11-334 on melanoma cells of A375 and MUG Mel1, whereas only minor effect on the dermal fibroblasts NHDF was observed, yielding an about 20-fold killing-specificity for A375 and MUG-Mel1. The LC50 values for melanoma A375 and MUG Mel1 were about 10 μM. Analysis of secondary structure of the peptide revealed an increase in the proportion of β-sheets exclusively in presence of the cancer mimic. Stability studies further indicated a potential adequate stability in blood or under stringent conditions. Importantly the cytotoxic effect on cancer cells was also proven in vivo in mouse xenografts of human melanoma, where peptide treatment induced strong tumor regression and in average a tumor area reduction of 85% compared to tumors of control mice without peptide treatment.

Although previous decades contributed to major progress in targeted therapy of many malignancies, the treatment of gynaecological cancers remains a challenging task. In the evidence of rising cancer mortality, the search for new methods of treatment is a dire need. Exploring the mechanisms of interaction between tumour cells and host immune response may allow the introduction of new, effective therapies – not as toxic and far more efficient than conventional methods of cancer treatment. Epithelial ovarian cancer (EOC) is typically diagnosed at advanced stages. Its incidence and mortality rate is high. Powerful diagnostic tools for this kind of cancer are still under investigation. Multiple mechanisms existing in the ovarian tumour network create a specific immunosuppressive microenvironment, in which accumulation of myeloid-derived suppressor cells (MDSCs) may be a critical component for diagnosis and treatment. This review attempts to verify current knowledge on the role of MDSCs in EOC.

Cancer incidence and mortality depend on a number of factors, including age, socio-economic status and geographical location, and its prevalence is growing around the world. Most of cancer treatments include external beam radiotherapy or brachytherapy. Brachytherapy, a type of radiotherapy with energy from radionuclides inserted directly into the tumor, is increasingly used in cancer treatment. For cervical and skin cancers, it has become a standard therapy for more than 100 years as well as an important part of the treatment guidelines for other malignancies, including head and neck, skin, breast, and prostate cancers. Compared to external beam radiotherapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time directly to the altered tissue area with the advantage of a rapid fall-off in dose, and consequently, sparing of adjacent organs. As a result, the patient is able to complete the treatment earlier, and the risks of occurrence of another cancer are lower than in conventional radiotherapy treatment. Brachytherapy has increased its use as a radical or palliative treatment, and become more advanced with the spread of pulsed-dose-rate and high-dose-rate afterloading machines; the use of new 3D/4D planning systems has additionally improved the quality of the treatment. The aim of the present study was to present short summaries of current studies on brachytherapy for the most frequently diagnosed tumors. Data presented in this manuscript should help especially young physicians or physicists to explore and introduce brachytherapy in cancer treatments.

// Sissel Hauge 1 , Christian Naucke 1 , Grete Hasvold 1 , Mrinal Joel 1 , Gro Elise Rodland 1 , Petras Juzenas 1 , Trond Stokke 1 , Randi G. Syljuasen 1 1 Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, N-0310, Norway Correspondence to: Randi G. Syljuasen, email: randi.syljuasen@rr-research.no Keywords: checkpoint kinase inhibitors, cancer treatment, replication stress, DNA damage, CDK activity Received: August 04, 2016 Accepted: December 15, 2016 Published: December 22, 2016 ABSTRACT Recent studies have shown synergistic cytotoxic effects of simultaneous Chk1- and Wee1-inhibition. However, the mechanisms behind this synergy are not known. Here, we present a flow cytometry-based screen for compounds that cause increased DNA damage in S-phase when combined with the Wee1-inhibitor MK1775. Strikingly, the Chk1-inhibitors AZD7762 and LY2603618 were among the top candidate hits of 1664 tested compounds, suggesting that the synergistic cytotoxic effects are due to increased S-phase DNA damage. Combined Wee1- and Chk1-inhibition caused a strong synergy in induction of S-phase DNA damage and reduction of clonogenic survival. To address the underlying mechanisms, we developed a novel assay measuring CDK-dependent phosphorylations in single S-phase cells. Surprisingly, while Wee1-inhibition alone induced less DNA damage compared to Chk1-inhibition, Wee1-inhibition caused a bigger increase in S-phase CDK-activity. However, the loading of replication initiation factor CDC45 was more increased after Chk1- than Wee1-inhibition and further increased by the combined treatment, and thus correlated well with DNA damage. Therefore, when Wee1 alone is inhibited, Chk1 suppresses CDC45 loading and thereby limits the extent of unscheduled replication initiation and subsequent S-phase DNA damage, despite very high CDK-activity. These results can explain why combined treatment with Wee1- and Chk1-inhibitors gives synergistic anti-cancer effects.

// Massimiliano Orri 1,2,* , Jordan Sibeoni 1,2,* , Guilhem Bousquet 3,4,5,6 , Mathilde Labey 1,2 , Juliette Gueguen 7 , Cyril Laporte 8,9 , Sabine Winterman 6 , Camille Picard 10,11 , Clara Nascimbeni 10,11 , Laurence Verneuil 10,11 and Anne Revah-Levy 1,2 1 Service Universitaire de Psychiatrie de l’Adolescent, Argenteuil Hospital Centre, Argenteuil, France 2 ECSTRA Team, UMR-1153, Inserm, Paris Diderot University, Sorbonne Paris Cite, Paris, France 3 Universite Paris Diderot, Sorbonne Paris Cite, Laboratoire de Pathologie, UMR-S 1165, Paris, France 4 INSERM, U1165-Paris, France 5 Universite Paris 1, Leonard de Vinci, Villetaneuse, France 6 AP-HP-Hopital Avicenne, Service d’Oncologie Medicale–Bobigny, Bobigny, France 7 Ecole Doctorale E420, Paris Saclay University, Paris, France 8 Centre de Cancerologie Paris Nord, Sarcelles, France 9 Recherche Innovation Sante Sarcelles, Sarcelles, France 10 Department of Dermatology, CHRU Caen, Caen, France 11 Caen Basse Normandie University, Caen, France * These authors have contributed equally to this article ** These authors are co-senior authors Correspondence to: Massimiliano Orri, email: // Keywords : patient-centered care, quality of life, care, qualitative study, crossed perspectives Received : June 11, 2016 Accepted : October 13, 2016 Published : October 19, 2016 Abstract Purpose. Patients, family members, and physicians participate in cancer care, but their perspectives about what is helpful during cancer treatment have rarely been compared. The aim of this study was to compare these three perspectives. Methods. Multicenter qualitative study (with previously published protocol) based on 90 semi-structured interviews. Participants (purposively selected until data saturation) came from three different subsamples: (i) patients with cancer (n=30), (ii) their relatives (n=30), and (iii) their referring physicians (n=10, interviewed more than once). Results. Our analysis found 3 main axes (perceived positive effects of cancer treatment, perceived negative effects of cancer treatment, doctor-physician relationship), each composed of 2 main themes. The findings showed that patients, families, and physicians shared the long-term objective of increasing survival (while reducing side effects). However, patients and relatives also pointed out the importance of living with cancer each day and thus of factors helping them to live as well as possible in daily life. The physicians’ difficulty in coping with patients’ suffering may limit their access to elements that can improve patients’ capacity to live as well as possible. Conclusions. During cancer treatment (and not only at the end of life), attention should be given to enhancing the capacity of patients to live as well as possible (not only as long as possible) to meet the goals of patient-centered care and satisfy this important need of patients and families.

Introduction: Menopause is defined as a 12-month period of time when menstruation permanently ceases. In some cases, menopause may be caused by external factors - for example gonadotoxic treatment that irreversibly damages ovarian tissue leading to loss of its hormonal and reproductive function. Oncofertility is a discipline that merges oncology and reproductive medicine, giving patients a chance to experience parenthood after gonadotoxic treatment is finished. Aim of the study: The purpose of the study is to present the implementation and first outcomes of the Oncofertility Programme in the University Clinic of Endocrinological Gynaecology and Gynaecology, University Hospital in Krakow, Poland. Material and methods: Patients interested in fertility preservation have been consulted in the University Clinic of Endocrinological Gynaecology and Gynaecology in Krakow since April 2016. Preliminary qualification to one of the available methods (embryo cryopreservation, oocyte cryopreservation, ovarian tissue cryopreservation) was conducted. Patients declaring a wish to join the programme were then referred to one of the three infertility treatment centres cooperating with the University Clinic, in order to undergo the chosen procedure. Results: During a period of 24 months, 18 patients were consulted. The youngest consulted patient was 20 years old, the oldest 39. Two years after the first consultation, a telephone survey among consulted patients was carried out to verify whether the patients finally underwent oncofertility procedures, and to ask about their reproductive status. Conclusions: The problem of fertility issues being inadequately addressed results in low referral rates to oncofertility programmes. Attempts to raise awareness of oncofertility possibilities among oncologists should be undertaken because critically few patients are being referred to oncofertility centres.

BackgroundA reproductive health implication of the increasing incidence of cancer among women is the impact of cancer treatment on fertility.ObjectiveAs patients are increasingly using the internet, particularly online forums, to seek and share experiences, our objective was to understand information needs about cancer treatment, fertility, and pregnancy of women with cancer as well as their caregivers.MethodsWe searched threads (original posts and responses) on four subreddit sites of Reddit (“r/Cancer,” “r/TryingForABaby,” “r/BabyBumps,” and “r/Infertility”) over a 5‐year period between February 4th, 2014 and February 4th, 2019. Threads with original posts involving a lived experience or question regarding cancer treatment and female fertility and/or pregnancy or parenting/having children from the perspective of either patient or caregiver were included in our analysis. We analyzed threads using thematic analysis.ResultsFrom 963 Reddit threads identified, 69 were analyzed, including 56 with original posts by women with cancer and 13 with original posts by caregivers. From threads made by patients, we identified themes on becoming a part of an online community, impacts of cancer treatment and fertility concerns on self and social relationships, making family planning decisions, and experiences with medical team. We also identified a theme on the impact of cancer treatment and fertility concerns on caregivers.ConclusionsReddit provided a rich pool of data for analyzing the information needs of women facing cancer. Our findings demonstrate the far-reaching impacts of cancer treatment and fertility on physical, mental, and psychosocial health for both patients and their caregivers.

Motivation: Combinatorial therapies have been under intensive research for cancer treatment. However, due to the large number of possible combinations among candidate compounds, exhaustive screening is prohibitive. Hence, it is important to develop computational tools that can predict compound combination effects, prioritize combinations and limit the search space to facilitate and accelerate the development of combinatorial therapies. Results: In this manuscript we consider the NCI-DREAM Drug Synergy Prediction Challenge dataset to identify features informative about combination effects. Through systematic exploration of differential expression profiles after single compound treatments and comparison of molecular structures of compounds, we found that synergistic levels of combinations are statistically significantly associated with compounds’ dissimilarity in structure and similarity in induced gene expression changes. These two types of features offer complementary information in predicting experimentally measured combination effects of compound pairs. Our findings offer insights on the mechanisms underlying different combination effects and may help prioritize promising combinations in the very large search space. Availability and Implementation: The R code for the analysis is available on https://github.com/YiyiLiu1/DrugCombination. Contact: hongyu.zhao@yale.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein we compare two NIR-light sources; light emitting diodes (LEDs) and Lasers, for their effectiveness in NIR-PIT. A photosensitizer, IRDye-700DX, conjugated to panitumumab (pan-IR700), was incubated with EGFR-expressing A431 and MDA-MB-468-luc cells. NIR-light was provided by LEDs or Lasers at the same light dose. Laser-light produced more cytotoxicity and greater reductions in IR700-fluorescence intensity than LED-light. Laser-light also produced more cytotoxicity in vivo in both cell lines. Assessment of super-enhanced permeability and retention (SUPR) effects were stronger with Laser than LED. These results suggest that Laser-light produced significantly more cytotoxic effects compared to LEDs. Although LED is less expensive, Laser-light produces superior results in NIR-PIT.

Based on the nationwide survey into inpatients' utilization of the health service covered by China's urban basic medical insurance from 2008 to 2010, we analyzed the use rate, cancer profile and combined use of anticancer Chinese patent medicines (CPMs) on 51,382 insured cancer patients by using statistical, bi-clustering and network methods. We found that 42.4% of 51,382 cancer patients used 33 anticancer CPMs, and 51.7% used 71 anticancer Western medicines (WMs). The CPMs were most often used in lung (52%) and nasopharynx (52%) cancer patients, and least in bladder cancer (21%) and leukemia of unspecified cell type (21%) patients. The cost per patient for all 33 anticancer CPMs was 2069RMB, lower than that of the WMs (3458RMB). The cancer profile of commonly used CPMs and WMs for the top 17 cancers (>500 sampled patients) were provided, indicating anticancer CPMs had a broad spectrum of cancers and lacked selectivity in cancer treatment (CPM mean CV = 49%; WM mean CV = 152%). Moreover, 24.8% of the cancer patients used both CPMs and WMs, and CPM-WM combined use networks were constructed for four major cancers. This first nationwide analysis revealed the use characteristics and herb-drug combined use patterns of insurance covered anticancer CPMs in China. The study offers valuable information to guide future studies of the precision, safety and standard use of CPMs.

This study investigated a remote symptom monitoring intervention to examine if older participants with cancer received a similar magnitude of benefit compared with younger adults with cancer. We analyzed a longitudinal symptom monitoring intervention for 358 participants beginning a new course of chemotherapy treatment in community and academic oncology practices. The study design was a randomized control trial; participants were randomized to the intervention or usual care, the intervention was delivered during daily automated coaching. Older adults with moderate and severe symptoms derived similar benefit as those adults younger than 60 years of age, adherence to the study protocol which involved daily calls was high. There was no significant difference between the 2 age categories; on average, older adult participants made 88% of expected daily calls and younger adult participants made 90% of expected daily calls. Our results challenge the perception that older adults are unwilling or unable to use a technological tool such as interactive voice response and suggest that patient utilization may be guided by other factors, such as ease of use and perceived benefit from the intervention.

Solid tumors are typically supplied nutrients by a network of irregular blood vessels. By targeting these vascular networks, it might be possible to hinder cancer growth and metastasis. Vascular disrupting agents induce intertumoral hemorrhaging, making photoacoustic (PA) imaging well positioned to detect bleeding due to its sensitivity to hemoglobin and its various states. We introduce a fractal-based numerical model of intertumoral hemorrhaging to simulate the PA signals from disrupted tumor blood vessels. The fractal model uses bifurcated cylinders to represent vascular trees. To mimic bleeding from blood vessels, hemoglobin diffusion from microvessels was simulated. In the simulations, the PA signals were detected by a linear array transducer (30 MHz center frequency) of four different vascular trees. The power spectrum of each beamformed PA signal was computed and fitted to a straight line within the −6-dB bandwidth of the receiving transducer. The spectral slope and midband fit (MBF) based on the fit decreased by 0.11 dB / MHz and 2.12 dB, respectively, 1 h post bleeding, while the y-intercept increased by 1.21 dB. The results suggest that spectral PA analysis can be used to measure changes in the concentration and spatial distribution of hemoglobin in tissue without the need to resolve individual vessels. The simulations support the feasibility of using PA imaging and spectral analysis in cancer treatment monitoring by detecting microvessel disruption.

Next-generation sequencing has produced a large quantity of DNA or RNA sequences related to the processes occurring within tumors and their microenvironment in a reasonable time and cost. These data have been used to guide the identification of neoantigens and to determine their specific T-cell receptors. Furthermore, adoptive T-cell therapy targeting neoantigens is under development for cancer treatment. In this review, we first provide an overview of sequencing technologies and the updated findings concerning neoantigens related to adoptive T-cell therapy and then summarize the methods and principles underlying the development of next-generation sequencing-based neoantigen-reactive T-cell therapy for cancer.

Immunotherapies have revolutionized cancer treatment. Immunotherapy is effective for the treatment of a wide range of cancer types and can mediate complete and durable tumor regression. Nonetheless, the field still faces many significant challenges, such as the need for personalized therapeutic strategies and better biomarkers, the difficulty of selecting the right combination therapy, and resistance to currently available immunotherapies. Both cancer and host immunity comprise significantly diverse and complex ecosystems, making immunogenomics an ideal field for functional genomics analysis. In this review, we describe the cancer-immunity cycle, how cancer cells manage to evade immune attack and the current hurdles in the path of cancer immunotherapy. Then, we discuss how functional genomics approaches can pave the way for more successful cancer immunotherapies.