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Abstract Introduction Breast cancer is one of the most important health problems in the world and affects a great number of women over the entire globe. This group of tumors rarely presents as bilateral disease and, when it does happen, normally occurs within the same histological type. We report a rare case of concurrent bilateral breast cancer with two different histology types, a breast carcinoma and a breast sarcoma, in a 42-year-old woman referred to our hospital. Case presentation A 42-year-old Caucasian woman admitted to our institute in August 1999, presented with a nodule in the left breast of 3.0 × 2.5 cm, and, in the right breast, one of 1.0 cm, suspected of malignancy and with a clinically negative armpit. Biopsies had revealed invasive mammary carcinoma (right breast) and sarcoma (left breast). She was submitted to bilateral modified radical mastectomy. A histological study showed an invasive mammary carcinoma degree II lobular pleomorphic type with invasion of seven of the 19 excised axillary nodes in the right breast and, in the left breast, a sarcoma of the mammary stroma, for which the immunohistochemistry study was negative for epithelial biomarkers and positive for vimentin. Later, she was submitted for chemotherapy (six cycles of 75 mg/m2 5-fluorouracil, epirubicin and cyclophosphamide) followed by radiotherapy of the thoracic wall and axillary nodes on the left. Hormone receptors were positive in the tumor of the right breast, and tamoxifen, 20 mg, was prescribed on a daily basis (five years) followed by letrozole, 2.5 mg, also daily (five years). She presented no sign of negative evolution in the last consultation. Conclusion The risk of development of bilateral breast cancer is about 1% each year within a similar histological type, but it is higher in tumors with lobular histology. In this case, the patient presented, simultaneously, two histologically distinct tumors, thus evidencing a rare situation.

Introduction: Advanced malignant melanoma is a very aggressive disease, historically with poor prognosis before the new advances with immunotherapy and targeted therapies that have changed the standard of care, especially in cutaneous melanoma. Peru has aggressive features such as higher rates of acral lentiginous melanoma (ALM) subtype with historically shorter survival., Methods: This study describes Peruvian patients with advanced melanoma treated with immunotherapy (nivolumab) in two oncological institutions (public and private), including the discussion of the impact on overall survival (OS) divided by subtype (with incidence in ALM histology) and potential biomarkers that could be related to prognosis., Results: We found that immunotherapy is safe, and improves progression-free survival (PFS), OS and objective response rate (ORR) in our patients, with lower benefit in ALM histology. No prognostic blood inflammatory biomarkers were detected., Discussion: There is very limited data of Peruvian patients with metastatic melanoma treated with immunotherapy, especially the outcomes in ALM histology. Our goal is to share an example of the impact of immunotherapy in a Latin American (LATAM) population considered as an unsatisfied group with an enormous need of novel treatments and biomarkers., Competing Interests: Dr Alfonso Berrocal reports personal fees, BMS, personal fees, Novartis, personal fees, from MSD, personal fees, from Pierre Fabre, outside the submitted work. The author(s) report no financial or other conflict of interest in this work., (© 2024 Valencia et al.)

Triple-negative breast cancer (TNBC) comprises 15-20% of all breast cancers (BC). Lacking targeted therapy options, TNBC becomes the focal point of clinical investigations aiming not only to identify drugs with enhanced response potential but also to uncover new immunological and/or metabolic pathways conducive to more effective treatments. Currently, neoadjuvant treatment for TNBC relies on standard chemotherapy in conjunction with immunotherapy, given the improved response observed with this drug combination. This review delves into the latest therapeutic updates in TNBC treatment and explores potential advancements shaping the future landscape of this disease in the neoadjuvant setting.

The introduction of immunotherapy has brought about a paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). It has not only significantly improved the prognosis of patients but has also become a cornerstone of treatment, particularly in those without oncogenic driver mutations. Immune checkpoint inhibitors (ICIs) play a crucial role in the treatment of lung cancer and can be classified into two main groups: Anti-cytotoxic T lymphocyte antigen-4 (Anti-CTLA-4) and anti-T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti-PD-L1). Certainly, the landscape of approved first line immunotherapeutic approaches has expanded to encompass monotherapy, immunotherapy-exclusive protocols, and combinations with chemotherapy. The complexity of decision-making in this realm arises due to the absence of direct prospective comparisons. However, a thorough analysis of the long-term efficacy and safety data derived from pivotal clinical trials can offer valuable insights into optimizing treatment for different patient subsets. Moreover, ongoing research is investigating emerging biomarkers and innovative therapeutic strategies that could potentially refine the current treatment approach even further. In this comprehensive review, our aim is to highlight the latest advances in immunotherapy for advanced NSCLC, including the mechanisms of action, efficacy, safety profiles, and clinical significance of ICI.

Background and Objective: The therapeutic landscape for non-small cell lung cancer (NSCLC) has evolved considerably in the last few years. The targeted drugs and molecular diagnostics have been developed together at a fast pace. This narrative review explores the evolution of anaplastic lymphoma kinase (ALK) targeting therapies from discovering the ALK protein, molecular tests, present clinical trial data and future perspectives. Since the body of evidence on lung cancer is growing daily, most oncologists need time to implement data in their daily practice., Methods: We developed a narrative review to provide up-to-date help in the clinical decision-making of ALK-altered NSCLC patients. In 2022, the authors reviewed PubMed's published pivotal randomized Phase 3 trial results., Key Content and Findings: The development of ALK inhibitors was a revolution that is still ongoing; second and third-generation ALK inhibitors provided more than 30 months of progression-free survival (PFS) and impressive "brain-control". Brigatinib provided a survival benefit for patients with baseline brain metastases (HR 0.43, 95% CI: 0.21-0.89), and Lorlatinib demonstrated intracranial response rates of 82%, with 71% of complete intracranial responses. Personalized medicine is the new paradigm, from performing broad genetic panels for diagnosis to individual targeted therapy or combinations of different targeted agents., Conclusions: In the future, performing broad molecular panels should be the standard of care in the front line and after each progression to detect arising resistance mechanisms. Longer PFS will substantially convert a deadly condition into an almost chronic disease in the following decades. Treatment sequencing will be the cornerstone for patient survival, and liquid biopsies may replace tissue biopsies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-619/coif). CGL is employed by Bristol Myers Squibb. RADM serves as an unpaid editorial board member of Translational Lung Cancer Research from January 2020 to December 2023. RADM declares on the advisory board for Takeda; scientific sponsorship from Merck, Bayer and Pfizer; speaker fee from Novartis, Eurofarma, MSD, Astellas, and Astrazeneca; leadership for European School of Oncology. The other authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

Background: The COVID-19 pandemic caused discontinuities in cancer care (CC) in most countries. Here, the authors describe the real-world impacts of implementing a contingency plan employing telemedicine for CC. Methods: A retrospective study of patients who received CC through telemedicine at the Instituto Nacional de Enfermedades Neoplasicas, Peru, from March 2020 to February 2021 was conducted. Impacts were measured by comparing the amount of CC administered during the pandemic versus the prior year. Results: A total of 16,456 telemedicine visits were carried out. An annual comparative analysis showed a gap of 23% and telemedicine accounted for 27.6% of the total CC administered during the pandemic. A high (4.50/5) level of patient satisfaction with telemedicine was reported. Conclusion: Telemedicine is an important tool to facilitate the continuity of CC.

Cutaneous sarcomas are a heterogeneous group of rare mesenchymal neoplasms representing less than 1% of malignant tumors. Histology report remains the cornerstone for the diagnosis of these tumors. The most important clinicopathologic parameters related to prognosis include larger tumor size, high mitotic index, head and neck location, p53 mutations, depth of infiltration and histological grade, vascular and perineural invasion as well as the surgical margins status. Applying advanced biopsy techniques might offer more precise assessment of surgical margins, which constitutes a significant precondition for the management of these tumors. The management of cutaneous soft tissue sarcomas requires a multidisciplinary approach. Surgery remains the standard treatment, nonetheless adjuvant therapy may be required, consisting of radiotherapy, chemotherapy, and molecular targeted therapies to improve treatment outcomes. The role of molecular profiling in the treatment of uncontrolled disease is promising, but it may be offered to a relatively small proportion of patients and its use is still considered experimental in this setting. Due to the rarity of the disease, there is a need for knowledge and experience to be shared, pooled, organized and rationalized so that recent developments in medical science can have a major impact on the disease course. Multicenter clinical trials are needed to improve the care of patients with cutaneous sarcomas., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Metabolic reprogramming is an emerging cancer feature that has recently drawn special attention since it promotes tumor cell growth and proliferation. However, the mechanism of the Warburg effect is still largely unknown. This research aimed to reveal the effects of BarH-like homeobox 2 ( BARX2 ) in regulating tumor progression and glucose metabolism in lung adenocarcinoma (LUAD)., Methods: Expression of BARX2 was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in LUAD cell line and tissues, and the tumor-promoting function of BARX2 in LUAD cells was detected in vitro and in vivo xenograft models. The metabolic effects of BARX2 were examined by detecting glucose uptake, the production levels of lactate and pyruvate, and the extracellular acidification rate (ECAR). Chromatin immunoprecipitation (ChIP) assay and luciferase reporter gene assay were used to identify the underlying molecular mechanism of BARX2 regulation of HK2 . Further studies showed that transcription factor FOXA1 directly interacts with BARX2 and promotes the transcriptional activity of BARX2 ., Results: BARX2 was remarkably up-regulated in LUAD tissues and positively linked to advanced clinical stage and poor prognosis. In vitro and in vivo data indicated ectopic expression of BARX2 enhanced cell proliferation and tumorigenesis, whereas BARX2 knockdown suppressed these effects. Metabolic-related experiments showed BARX2 promoted the reprogramming of glucose metabolism. Mechanistically, the BARX2/FOXA1/HK2 axis promoted LUAD progression and energy metabolism reprogramming., Conclusions: In summary, our research first defined BARX2 as a tumor-promoting factor in LUAD and that it may act as a novel prognostic biomarker and new therapeutic target for the disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-465/coif). Prof. RAdM received research grant from CNPQ Brazil, Libss, Pfizer; royalties from Springer; consulting fee from Takeda; speaker fee from Merck, Pfizer, Novartis, Eurofarma, MSD, Bayer, Astrazenenca; supporting for attending meetings and stock from Merck. Prof. RAdM also serves in Advisory board for European School of Oncology and Brazilian Society of Cancerology. ACR received Royalties from educational material for thymic tumors; payment from Honorarium for grand rounds at NY Langone; and Travel support for visiting professorship at NYU Langone; none of them are pertinent to this publication. The other authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Background: Management of Ras wild-type colorectal cancer (CRC) patients upon disease progression after the successful use of targeted treatment with anti-EGFR monoclonal antibodies and backbone chemotherapy remains a clinical challenge., Summary: Development of treatment resistance with prevalence of preexisting RAS mutated clones, RAS mutation conversion, truncation of extracellular receptor domains as well as HER2 and MET amplification are molecular events that can be difficult to follow without the use of sophisticated laboratory techniques. The clinical hurdle of re-biopsy and tumor heterogeneity can be overcome by the implementation of next-generation sequencing (NGS) to analyze circulating tumor DNA (ctDNA) and identify druggable mutations or recovery of RAS-wildness. In this opinion paper, we summarize with critical thinking the clinical approach to be followed after the failure of first-line treatment in Ras wild-type CRC tumors with the use of NGS. Rechallenge with anti-EGFR inhibitors, in case of persistent or recovery of RAS-wildness, and targeted approach of specific mutations (BRAF inhibitors), amplifications (anti-Her2 treatment), or fusion proteins (NTRK inhibitors) can by guided by the use of NGS. The use of NGS platforms for serial analysis of ctDNA is an important step to better understand the molecular landscape of metastatic CRC and guide clinical decisions., Key Messages: NGS should be considered a mainstay in clinical practice for the management of CRC patients and health authorities should consider reimbursing its use in the appropriate clinical settings., (© 2022 S. Karger AG, Basel.)

Background: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations., Methods: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries., Results: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population., Conclusion: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: "Screening", "Diagnosis", and "Biomarkers for CRC". American and European clinical trials in progress were included as well.

Gastric cancer is the fourth most common type of cancer worldwide and the second most lethal. Gastric cancer biomarkers can be used for diagnosis, prediction of sensitivity to treatment, and prognosis. The following search terms were applied to PubMed as of December 2020: 'gastric cancer classification', 'gastric cancer epidemiology', 'cancer metastasis' and 'gastric cancer biomarker'. Only experimental studies were reported in the 'biomarkers' section. Some biomarkers can serve as therapeutic targets for antitumoral drugs. The genes analyzed include E-cadherin, RPRM , XAF1 , MINT25 , TFF1 , p16 and p53 . The miRNAs analyzed include miR-18a, miR185-5p, miR-125b and miR-21. Some molecules were associated with metastasis of gastric cancer, specifically those involved with EMT process and tissue degradation.

Purpose: CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases., Methods: We searched Pubmed and Google Scholar for CRISPR-based strategies in the diagnosis and treatment of infectious diseases. Reference lists were reviewed and synthesized for narrative review., Results: CRISPR-based strategies represent a novel approach to many challenging infectious diseases. CRISPR technologies can be harnessed to create rapid, low-cost diagnostic systems, as well as to identify drug-resistance genes. Therapeutic strategies, such as CRISPR systems that cleave integrated viral genomes or that target resistant bacteria, are in development. CRISPR-based therapies for emerging viruses, such as SARS-CoV-2, have also been proposed. Finally, CRISPR systems can be used to reprogram human B cells to produce neutralizing antibodies. The risks of CRISPR-based therapies include off-target and on-target modifications. Strategies to control these risks are being developed and a phase 1 clinical trials of CRISPR-based therapies for cancer and monogenic diseases are already underway., Conclusions: CRISPR systems have broad applicability in the field of infectious diseases and may offer solutions to many of the most challenging human infections.

Background: The coexistence of chronic obstructive pulmonary disease (COPD) in lung cancer patients often correlates with a poor clinical outcome regardless of tumor stage, mainly due to older age, poor lung function, and complex comorbid disease. Emerging data suggest that the pathogenesis of both diseases involves aberrant immune functioning. We conducted this retrospective study to describe the impact of COPD on the clinical outcomes of lung cancer patients treated with immunotherapy and investigate the potential prognostic factors., Methods: In total, 156 patients with advanced-stage lung cancer who received at least one administration of an anti-programmed cell death 1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) at any treatment line at Zhongshan Hospital Fudan University between May 2018 and December 2019 were enrolled in our study. Overall survival (OS) and progression-free survival (PFS) were analyzed according to the presence of COPD. We also evaluated the prognostic value of circulating cytokine levels for clinical outcome., Results: We found that the presence of COPD (both spirometry-based COPD and physician-defined COPD) was significantly associated with longer PFS (316 vs. 186 days, P=0.018). Moderate and severe COPD tended to have a better impact on the survival of these patients. In the present study, we reported that patients with mixed ventilatory defects tended to have a better OS (P=0.043) and PFS (P=0.18) when treated with ICIs compared to the normal lung function group. We also found that low baseline plasma interleukin (IL)-8 and IL-2 receptor (IL-2R) levels were associated with longer PFS in patients with advanced-stage lung cancer who received ICI treatment. Furthermore, patients who had increased IL-2R levels had significantly poorer OS [hazard ratio (HR) =3.63; 95% confidence interval (CI), 0.98-13.44; P=0.040] and PFS (HR =3.241; 95% CI, 1.032-10.18; P=0.035) when treated with ICIs. Nomograms were established based on the independent prognostic factors derived from our final multivariate models., Conclusions: COPD was associated with better survival in advanced-stage lung cancer patients treated with ICIs. Plasma IL-8 and IL-2R levels were potential prognostic factors for clinical outcome. The nomograms represent a possibly useful tool for predicting the clinical outcomes of immunotherapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-21-214). The authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Introduction: Pandemic COVID-19 is an unexpected challenge for the oncological community, indicating potential detrimental effects on cancer patients. Our aim was to summarize the converging key points providing a general guidance in order to support decision making, pertaining to the oncologic care in the middle of a global outbreak., Methods: We did an international online search in twenty five countries that have managed a surge in cancer patient numbers. We collected the recommendations from thirty one medical oncology societies., Results: By synthesizing guidelines for a) oncology service delivery adjustments, b) general and specific treatment adaptations, and c) discrepancies from guidelines comparison, we present a clinical synopsis with the forty more crucial statements. A Covid-19 risk stratification base was also created in order to obtain a quick, objective patient assessment and a risk-benefit evaluation on a case-by-case basis., Conclusions: In an attempt to face these complex needs and due to limited understanding of COVID-19, a variability of recommendations based on general epidemiological and infectious disease principles rather than definite cancer-related evidence has evolved. Additionally, the absence of an effective treatment or vaccine requires the development of cancer management guidance, capitalizing on comprehensive COVID-19 oncology experience globally., (Copyright © 2020 Kamposioras, Mauri, Papadimitriou, Anthoney, Hindi, Petricevic, Dambrosio, Valachis, Kountourakis, Kopecky, Kuhar, Popovic, Chilingirova, Zarkavelis, de Mello, Plavetić, Christopoulos, Mostert, Goffin, Tzachanis, Saraireh, Ma, Pavese and Tolia.)

Introduction: Lung cancer (LC) is the most common neoplasm worldwide, and 85% of these tumors are classified as non-small cell lung cancer (NSCLC). LC treatment was initially restricted to cytotoxic chemotherapy-platinum compounds associated with 3rd generation cytotoxic agents (paclitaxel, gemcitabine, pemetrexed) and, more recently, with monoclonal antibodies (bevacizumab, ramucirumab). Advancements in treatment are correlated with prolonged overall survival (OS). Current advances are focused on target therapies. Target agents: Anti-epidermal growth factor receptor (EGFR) therapy consists of 1st and 2nd generation tyrosine kinase inhibitors (TKIs such as erlotinib, afatinib). In 60% of cases, resistance to these TKIs occurs due to T790M mutation in EGFR, which is overcome 3rd generation drugs (osimertinib). Anaplastic lymphoma kinase (ALK) is the target for drugs such as crizotinib, alectinib, ceritinib. Programmed death 1 (PD-1) and its ligand serve as targets for immunotherapy agents such as pembrolizumab, nivolumab, atezolizumab., Discussion: Challenges in NSCLC treatment include resistance to 3rd generation TKIs, the high cost of ALK inhibitors, and the need for further research on new drugs.

Background: Lung cancer (LC) development is a process that depends on genetic mutations. The DNA methylation, an important epigenetic modification, is associated with the expression of non-coding RNAs, such as microRNAs. MicroRNAs are particularly essential for cell physiology, since they play a critical role in tumor suppressor gene activity. Furthermore, epigenetic disruptions are the primary event in cell modification, being related to tumorigenesis. In this context, microRNAs can be a useful tool in the LC suppression, consequently improving prognosis and predicting treatment., Conclusion: This manuscript reviews the main microRNAs involved in LC and its potential clinical applications to improve outcomes, such as survival and better quality of life., (© 2020 Bentham Science Publishers.)

Introduction : Non-small cell lung cancer (NSCLC) is the second most common cancer globally. The mesenchymal-epithelial transition (MET) proto-oncogene can be targeted in NSCLC patients. Methods : We performed a literature search on PubMed in December 2019 for studies on MET inhibitors and NSCLC. Phase II and III clinical trials published in English between 2014 and 2019 were selected. Results : Data on MET inhibitors (tivantinib, cabozantinib, and crizotinib) and anti-MET antibodies (emibetuzumab and onartuzumab) are reported in the text. Conclusion : Emibetuzumab could be used for NSCLC cases with high MET expression. Further, studies on onartuzumab failed to prove its efficacy, while the results of tivantinib trials were clinically but not statistically significant. Additionally, cabozantinib was effective, but adverse reactions were common, and crizotinib was generally well-tolerated.

Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. The study aimed to investigate the effects and molecular mechanism of miR-139-5p/SLC7A11 on the proliferation and metastasis of PANC., Methods: Bioinformatics was used to analyze the differentially expressed genes in the TCGA database. PANC cell lines with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and have been used to detect cell proliferation, invasion and metastasis of PANC Subsequently, bioinformatic analysis and dual luciferase reporter assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mice model was used to explore the functions of miR-139-5p in PANC tumorigenicity., Results: MiR-139-5p could regulate and affect the protein expression of P13K and Akt associated with phosphatidylinositol signaling pathway by inhibiting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, invasion and metastasis could be inhibited by miR-139-5p overexpression and be promoted by SLC7A11 overexpression. MiR-139-5p overexpression could suppress PANC tumor growth and the expressions of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibitory of miR-139-5p to PANC cell proliferation, invasion and metastasis was partly due to its inhibiting effect on SLC7A11 expression., Conclusion: Our study proves that miR-139-5p/SLC7A11 has important functions on PANC, suggesting that miR-139-5p can be used as a biomarker for PANC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Esophagogastric (EG) cancer has a poor prognosis despite the use of standard therapies, such as chemotherapy and biologic agents. Recently, immune checkpoint inhibitors (ICIs) have been introduced as treatments for EG cancer; nivolumab and pembrolizumab have been approved in the United States and Europe to treat advanced EG cancer. Other ICIs, such as avelumab, durvalumab, ipilimumab, and tremelimumab, have been evaluated in several trials, although their roles are still not established in clinical practice. In addition, preclinical evidence suggests that combining an ICI with a tumor-targeting antibody can result in greater antitumor effects in metastatic EG cancer. There are not yet validated predictive biomarkers to identify which patients will respond best to ICI treatment. PD-L1 expression may predict intensity of response, although PD-L1-negative patients can still respond to ICIs. Despite differences in PD-L1 expression between Asian and non-Asian populations, no geographic differences in rates of treatment-related or immune-mediated/infusion-related adverse events have been reported. Also, several trials are currently evaluating combinations of ICIs, standard chemotherapy, and biologic agents as well as novel biomarkers to improve treatments and outcomes. Our review will address the current use of and evidence for ICIs for advanced EG cancer treatment and future trends in this area for clinical practice.

Aim: Immune checkpoint inhibitors revolutionized the treatment of non-small-cell lung cancer, although their costs are a limitation., Methods: The number of patients with non-small-cell lung cancer eligible for immunotherapy was estimated using local epidemiology data. We extracted survival data from RCTs to estimate the life-years saved in a 5-year time horizon. All costs were in local prices converted to US dollars., Results: In the first-line, the budget impact of pembrolizumab decreased by 35% through risk-sharing. In the second-line, patient selection by programmed-death receptor ligand 1 expression decreased the budgetary impact by 45%, and improved cost-effectiveness. Immunotherapy was more cost-effective in the first-line., Conclusion: Given current pricing, Immune checkpoint inhibitors are cost-prohibitive in the majority of South American health services. Nevertheless, several strategies should improve access to immunotherapy.

Esophageal cancer and gastric cancer are aggressive diseases for which treatment approaches are facing a new era. Some molecular pathways, such as VEGF, EGFR, fibroblast growth factor receptor, PIK3CA, and PARP-1, have been studied, and novel targeted drugs are presumed to be developed in the near future. From The Cancer Genome Atlas report, 80% of Epstein-Barr virus tumors and 42% of tumors with microsatellite instability have PIK3CA mutations, suggesting that this pathway could be reevaluated as a possible target for new systemic treatment of gastric cancer. Notably, higher PARP-1 expression can be found in gastric cancer, which might be related to more advanced disease and worse prognosis. In addition, PD-L1 expression, high microsatellite instability, and mismatch repair deficiency can be found in gastric cancer, thus suggesting that immunotherapy may also play a role in those patients. We discuss trends related to the potential of novel therapies for patients with esophageal and gastric cancers in the near future.

The global burden of lung cancer has been increasing over the past years, and is still a major threat to public health worldwide, leading to disabilities and premature mortality. Despite multifactorial cause, smoking remains as the major etiological factor, followed by occupational exposure to carcinogens, genetic predisposition and other concomitant diseases. In order to reduce the individual and social burden due to the direct and indirect costs related to the lung cancer treatment, accurate methods of screening are needed. Among those, x-ray with cytological analysis of sputum was first proposed. Nowadays, more sensitive methods such as low-dose computed tomography are being used to improve the early detection. In the future, molecular biomarkers may complement low-dose computed tomography and improve the robustness of early lung cancer detection.

Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small-cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection., Materials and Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC. Cochrane guidelines were used for statistical analysis., Results: 3,179 patients were included. All EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR for gefitinib, erlotinib and afatinib were 52.1%, 67.3% and 61.6% respectively. HRs for PFS were 0.62 (95% CI, 0.38-1.00) for gefitinib, 0.28 (95% CI, 0.17-0.45) for erlotinib and 0.40 (95% CI, 0.20-0.83) for afatinib. HRs for OS were not statistically significant for any agent., Conclusions: Our results suggest similar clinical efficacy and higher toxicity of Afatinib treatment. As this still remains the agent with best CSF penetration, we suggest its use is limited to patients presenting with brain metastasis. We suggest the use of Gefitinib in patients without CNS involvement. Faced with the impossibility to dose-reduce Gefitinib, Erlotinib represents a tolerable and effective alternative to Afatinib and Gefitinib if response to EGFR inhibition is considered still effective., Competing Interests: CONFLICTS OF INTEREST RAM has received honoraria from Pfizer Advisory Board, Zodiac advisory board, AstraZeneca, Novartis, National Science Centre, Krakow, Poland, and educational grant from Pierre Fabre, Amgem. RAM is ad hoc consultant at Ministry of Health, Brasília, Brazil. The other authors have no conflicts of interest in this manuscript. GM has received honoraria from Bristol Myers Squibb, Roche and AstraZeneca.

Aim: We explore the biomarker potential of the TERT hypermethylated oncologic region (THOR) in pancreatic cancer., Materials & Methods: We assessed the methylation status of THOR using the cancer genome atlas data on the cohort of pancreatic cancer (n = 193 patients)., Results: THOR was significantly hypermethylated in pancreatic tumor tissue when compared with the normal tissue used as control (p < 0.0001). Also, THOR hypermethylation could distinguish early stage I disease from normal tissue and was associated with worse prognosis., Discussion:  We found that THOR is hypermethylated in pancreatic tumor tissue when compared with normal tissue and that THOR methylation correlates with TERT expression in tumor samples., Conclusion: Our preliminary findings support the diagnostic and prognostic values of THOR in pancreatic cancer.

Lung cancer (LC) is a serious public health problem responsible for the majority of cancer deaths and comorbidities in developed countries. Tobacco smoking is considered the main risk factor for LC; however, only a few smokers will be affected by this cancer. Current screening methods are focused on identifying the early stages of this malignancy. Thus, new data concerning the roles of microRNA alterations in inflammation, epithelial-mesenchymal transition and lung disease have increased hope about LC pathogenesis, diagnosis, treatment and prognosis. MicroRNA mechanisms include angiogenesis promotion, cell cycle regulation by modulating cellular proliferation and apoptosis, and migration and invasion inhibition. In this context, this manuscript reviews the current information about many important microRNAs as they relate to the initiation and progression of LC., Competing Interests: CONFLICTS OF INTEREST R.A. De Mello is on the advisory board for Pfizer and Zodiac and is a speaker for AstraZeneca and Novartis. The authors declare that they have no conflicts of interest.

Background: Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection., Design: We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment., Results: We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy., Conclusion: The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Lung cancer is the leading cause of cancer-related deaths in the world. Immune checkpoint inhibitors (ICI) stimulate cytotoxic lymphocyte activity against tumour cells. These agents are available for the treatment of non-small cell lung cancer (NSCLC) after failure of platinum-based therapy. One recent study has demonstrated that ICI monotherapy was superior to platinum-based chemotherapy for first-line treatment. Nevertheless, this benefit was only for a minority of the population (30%) whose tumour programmed death receptor ligand-1 (PD-L1) expression was above 50%. Therefore, several strategies are under investigation. One option for patients with PD-L1 expression lower than 50% may be the combination of ICI with platinum-based chemotherapy or with ICIs against different targets. However, all of these combinations are at an early stage of investigation and may be very expensive or toxic, producing several harmful adverse events., Competing Interests: Competing interests: None declared.

Aim: The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is PD-L1 expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data., Methods: We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis., Results: 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89)., Conclusion: PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.