Search

The cancer stem cell (SC) theory proposes that a population of SCs serves as the driving force behind fundamental tumor processes, including metastasis, recurrence, and resistance to therapy. The standard of care for patients with stage III and high-risk stage II colorectal cancer (CRC) includes surgery and adjuvant chemotherapy. Fluoropyrimidines and their combination with oxaliplatin increased the cure rates, being able to eradicate the occult metastatic SC in a fraction of patients. The treatment for unresectable metastatic CRC is based on chemotherapy, antibodies to VEGF and EGFR, and tyrosine-kinase inhibitors. Immunotherapy is used in MSI-H tumors. Currently used drugs target dividing cells and, while often effective at debulking tumor mass, these agents have largely failed to cure metastatic disease. SCs are generated either due to genetic and epigenetic alterations in stem/progenitor cells or to the dedifferentiation of somatic cells where diverse signaling pathways such as Wnt/β-catenin, Hedgehog, Notch, TGF-β/SMAD, PI3K/Akt/mTOR, NF-κB, JAK/STAT, DNA damage response, and Hippo-YAP play a key role. Anti-neoplastic treatments could be improved by elimination of SCs, becoming an attractive target for the design of novel agents. Here, we present a review of clinical trials assessing the efficacy of targeted treatment focusing on these pathways in CRC. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes (T1Ds) is an autoimmune disease in which the immune system invades and destroysinsulin-producing cells. Nevertheless, at the time of diagnosis, about 30-40% of pancreatic beta cells are healthy andcapable of producing insulin. Bi-specific antibodies, chimeric antigen receptor regulatory T cells (CAR-Treg cells), andlabeled antibodies could be a new emerging option for the treatment or diagnosis of type I diabetic patients. The aimof the study is to choose appropriate cell surface antigens in the pancreas tissue for generating an antibody for type Idiabetic patients.Materials and Methods: In this bioinformatics study, we extracted pancreas-specific proteins from two largedatabases; the Human Protein Atlas (HPA) and Genotype-Tissue Expression (GTEx) Portal. Pancreatic-enrichedgenes were chosen and narrowed down by Protter software for the investigation of accessible extracellular domains.The immunohistochemistry (IHC) data of the protein atlas database were used to evaluate the protein expression ofselected antigens. We explored the function of candidate antigens by using the GeneCards database to evaluate thepotential dysfunction or activation/hyperactivation of antigens after antibody binding.Results: The results showed 429 genes are highly expressed in the pancreas tissue. Also, eighteen genes encodedplasma membrane proteins that have high expression in the microarray (GEO) dataset. Our results introduced fourstructural proteins, including NPHS1, KIRREL2, GP2, and CUZD1, among all seventeen candidate proteins.Conclusion: The presented antigens can potentially be used to produce specific pancreatic antibodies that guide CARTreg,bi-specific, or labeling molecules to the pancreas for treatment, detection, or other molecular targeted therapyscopes for type I diabetes.

Primary central nervous system lymphomas (PCNSL) are rare highly aggressive diffuse large B cell non-Hodgkin lymphomas confined to the brain, meninges, the spinal cord and the eyes. Although the implementation of high-dose methotrexate-based chemotherapy has significantly improved the prognosis of PCNSL during the last decades, about one third of patients show refractory disease and about half of the patients eventually relapse after having achieved complete response. This highlights the need for novel treatment strategies. The most promising progress has been made in the field of molecular targeted therapy that interferes with the oncogenic signaling pathways of PCNSL. These include inhibitors of Bruton tyrosine kinase and inhibitors of the PI3K/mTOR signaling pathway. In addition, the thalidomide analogues lenalidomide and pomalidomide, which belong to the class of immunomodulators, show efficacy in the treatment of PCNSL. As immune evasion appears to play a relevant pathogenetic role in PCNSL, immunotherapies in the treatment of PCNSL are the subject of intensive research. Promising initial clinical data are available for both immune checkpoint inhibitors and cellular immunotherapy with chimeric antigen receptor (CAR) T cells. Before the widespread clinical application of these novel therapies, the efficacy needs to be confirmed in larger prospective studies. Despite high response rates, targeted therapies and immunotherapy often fail to achieve lasting tumor control. Therefore, novel approaches are currently being investigated in combination protocols. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper delves into the latest developments in the emerging therapies for cholangiocarcinoma, with a focus on precision medicine, immunotherapy, and targeted therapies. We explore the potential of genomic profiling to tailor treatments to individual patients, as well as the promising results of immunotherapeutic agents in clinical trials. Furthermore, we examine the role of specific molecular targets and their inhibitors in slowing disease progression. The findings discussed in this paper offer hope for improved outcomes and prolonged survival in cholangiocarcinoma patients using more effective and personalized treatment strategies. Cholangiocarcinoma is a heterogeneous group of biliary tract cancers that has a poor prognosis and globally increasing incidence and mortality. While surgical resection remains the only curative option for the treatment of cholangiocarcinoma, the majority of cancers are unresectable at the time of diagnosis. Additionally, the prognosis of cholangiocarcinoma remains poor even with the current first-line systemic therapy regimens, highlighting the difficulty of treating locally advanced, metastatic, or unresectable cholangiocarcinoma. Through recent developments, targetable oncogenic driver mutations have been identified in the pathogenesis of cholangiocarcinoma, leading to the utilization of molecular targeted therapeutics. In this review, we comprehensively discuss the latest molecular therapeutics for the treatment of cholangiocarcinoma, including emerging immunotherapies, highlighting promising developments and strategies. [ABSTRACT FROM AUTHOR]

Tattoo-associated cutaneous reactions have become quite frequent given the increasing percentage of tattooed subjects globally and also in Italy. On the other hand, the increasing use of target therapy is showing the ability of these drugs to affect the immune system and also cause adverse tattoo-related reactions. In this paper, we report a case of a 42-year-old patient with stage-IIID melanoma undergoing treatment with Dabrafenib and Trametinib. The patient reported erythema, oedema and scaling in areas of the body containing a black tattoo, and, conversely, no signs and/or symptoms in areas with tattoos of a different color. Histopathological and immunohistochemical features indicated a lympho-histiocytic reaction with a granulomatous morphology, mainly distributed around the vessels and hair adnexa. By discussing the cases reported in the literature prior to ours, we concluded and provided the possible indications of the pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes (T1Ds) is an autoimmune disease in which the immune system invades and destroys insulin-producing cells. Nevertheless, at the time of diagnosis, about 30-40% of pancreatic beta cells are healthy and capable of producing insulin. Bi-specific antibodies, chimeric antigen receptor regulatory T cells (CAR-Treg cells), and labeled antibodies could be a new emerging option for the treatment or diagnosis of type I diabetic patients. The aim of the study is to choose appropriate cell surface antigens in the pancreas tissue for generating an antibody for type I diabetic patients. Materials and Methods: In this bioinformatics study, we extracted pancreas-specific proteins from two large databases; the Human Protein Atlas (HPA) and Genotype-Tissue Expression (GTEx) Portal. Pancreatic-enriched genes were chosen and narrowed down by Protter software for the investigation of accessible extracellular domains. The immunohistochemistry (IHC) data of the protein atlas database were used to evaluate the protein expression of selected antigens. We explored the function of candidate antigens by using the GeneCards database to evaluate the potential dysfunction or activation/hyperactivation of antigens after antibody binding. Results: The results showed 429 genes are highly expressed in the pancreas tissue. Also, eighteen genes encoded plasma membrane proteins that have high expression in the microarray (GEO) dataset. Our results introduced four structural proteins, including NPHS1, KIRREL2, GP2, and CUZD1, among all seventeen candidate proteins. Conclusion: The presented antigens can potentially be used to produce specific pancreatic antibodies that guide CAR- Treg, bi-specific, or labeling molecules to the pancreas for treatment, detection, or other molecular targeted therapy scopes for type I diabetes. [ABSTRACT FROM AUTHOR]

Hao-Huan Tang,1,&ast; Ming-Qing Zhang,2,&ast; Zi-Chen Zhang,3,&ast; Chen Fan,1 Yong Jin,2 Wei-Dong Wang1 1Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China; 2Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3Department of Interventional Vascular Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei, 230011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Jin, Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, No. 1055, Sanxiang Road, Suzhou, 215006, People’s Republic of China, Tel/Fax +86 512 67784269, Email jinyong@suda.edu.cn Wei-Dong Wang, Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299, Qingyang Road, Wuxi, 214023, People’s Republic of China, Tel/Fax +86 510 85350121, Email Wdoc@sina.comObjective: To investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) for intermediate and advanced HCC that are unsuitable for transarterial chemoembolization (TACE).Methods: We conducted a retrospective analysis of data from patients with TACE-unsuitable HCC who were receiving triple therapy from January 2020 to December 2021 at two medical centers. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rates (ORR), disease control rates (DCR), and incidence of adverse events (AEs).Results: A total of 55 patients were enrolled in the study with median treatment periods of 4 and 6 for HAIC and PD-(L)1 inhibitors, respectively. The median OS and PFS were 15.0 and 10.0 months, respectively, with a median follow-up of 11.0 months (range: 4.0– 27.5 months). According to the mRECIST criteria, the optimal ORR was 43.6% (24/55) and the DCR was 61.8% (34/55). The incidence of AEs was 58.2%, with grade 3 and above accounting for 20.0%; elevated AST (18.2%), hyperbilirubinemia (16.4%), and thrombocytopenia (16.4%) were most common. There were no treatment-related fatalities and all AEs were effectively managed. Multifactorial analysis showed that NLR > 3.82 (HR 2.380, 95% CI 1.116-2-5.079, P = 0.025), ECOG 1 (HR 2.906, 95% CI 1.373– 6.154, P = 0.005), and extrahepatic metastases (HR 8.373, 95% CI 3.492– 20.078, P < 0.001) were associated with the median OS.Conclusion: Triple therapy with HAIC, PD-(L)1 inhibitors, and MTT was safe and effective for patients with intermediate and advanced HCC for TACE-unsuitability.Keywords: advanced hepatocellular carcinoma, hepatic arterial infusion chemotherapy, molecular targeted therapies, PD-(L)1 inhibitors

Abstract Introduction The study aimed to optimize medical care for elderly patients with rheumatoid arthritis (RA) by examining the 3-year continuation rate of different molecular targeted therapies across age groups in Japan, which has a significant elderly population. Methods The study included patients with RA who started molecular targeted therapies between 2013 and 2019 and divided them into three age groups. The primary outcome was to assess the 3-year continuation rate of each drug and analyze reasons for treatment discontinuation using inverse probability of treatment weighting. Results Among 2292 patients analyzed, tumor necrosis factor (TNF) inhibitors were most commonly used in those younger than 65 years of age (43.5%), while Janus kinase (JAK) inhibitors were also utilized (17.1%). In contrast, JAK inhibitors were less frequently used in patients aged 75 years and older (7.8%), with cytotoxic T lymphocyte antigen 4 immunoglobulin fusion proteins (CTLA4-Ig) being the most common (39.2%). JAK inhibitors and anti-interleukin-6 receptor (IL-6R) antibodies had higher continuation rates than other drugs in patients under 65 years (p

Abstract With an average incidence of 1 in every 18,000 live births, retinoblastoma is a rare type of intraocular tumour found to affect patients during their early childhood. It is curable if diagnosed at earlier stages but can become life-threateningly malignant if not treated timely. With no racial or gender predisposition, or even environmental factors known to have been involved in the incidence of the disease, retinoblastoma is often considered a clinical success story in pediatric oncology. The survival rate in highly developed countries is higher than 95% and they have achieved this because of the advancement in the development of diagnostics and treatment techniques. This includes developing the already existing techniques like chemotherapy and embarking on new strategies like enucleation, thermotherapy, cryotherapy, etc. Early diagnosis, studies on the etiopathogenesis and genetics of the disease are the need of the hour for improving the survival rates. According to the Knudson hypothesis, also known as the two hit hypothesis, two hits on the retinoblastoma susceptibility (RB) gene is often considered as the initiating event in the development of the disease. Studies on the molecular basis of the disease have also led to deciphering the downstream events and thus in the discovery of biomarkers and related targeted therapies. Furthermore, improvements in molecular biology techniques enhanced the development of efficient methods for early diagnosis, genetic counseling, and prevention of the disease. In this review, we discuss the genetic and molecular features of retinoblastoma with a special emphasis on the mutation leading to the dysregulation of key signaling pathways involved in cell proliferation, DNA repair, and cellular plasticity. Also, we describe the classification, clinical and epidemiological relevance of the disease, with an emphasis on both the traditional and innovative treatments to tackle retinoblastoma. Video Abstract

Introduction: The study aimed to optimize medical care for elderly patients with rheumatoid arthritis (RA) by examining the 3-year continuation rate of different molecular targeted therapies across age groups in Japan, which has a significant elderly population. Methods: The study included patients with RA who started molecular targeted therapies between 2013 and 2019 and divided them into three age groups. The primary outcome was to assess the 3-year continuation rate of each drug and analyze reasons for treatment discontinuation using inverse probability of treatment weighting. Results: Among 2292 patients analyzed, tumor necrosis factor (TNF) inhibitors were most commonly used in those younger than 65 years of age (43.5%), while Janus kinase (JAK) inhibitors were also utilized (17.1%). In contrast, JAK inhibitors were less frequently used in patients aged 75 years and older (7.8%), with cytotoxic T lymphocyte antigen 4 immunoglobulin fusion proteins (CTLA4-Ig) being the most common (39.2%). JAK inhibitors and anti-interleukin-6 receptor (IL-6R) antibodies had higher continuation rates than other drugs in patients under 65 years (p < 0.001). For those aged 65–74 years, JAK inhibitors and CTLA4-Ig had higher continuation rates (p < 0.001), while among those aged 75 years and older, CTLA4-Ig and IL-6R antibodies had higher continuation rates (p < 0.001). Inadequate efficacy was the main reason for discontinuation in all age groups, while infection leading to discontinuation increased with age. Conclusions: The study highlights the need to consider different age groups separately in elderly RA care. Among patients aged 75 years and older, abatacept and anti-IL-6R antibodies showed the highest continuation rates, suggesting their potential suitability and efficacy for this specific age cohort. [ABSTRACT FROM AUTHOR]

With an average incidence of 1 in every 18,000 live births, retinoblastoma is a rare type of intraocular tumour found to affect patients during their early childhood. It is curable if diagnosed at earlier stages but can become life-threateningly malignant if not treated timely. With no racial or gender predisposition, or even environmental factors known to have been involved in the incidence of the disease, retinoblastoma is often considered a clinical success story in pediatric oncology. The survival rate in highly developed countries is higher than 95% and they have achieved this because of the advancement in the development of diagnostics and treatment techniques. This includes developing the already existing techniques like chemotherapy and embarking on new strategies like enucleation, thermotherapy, cryotherapy, etc. Early diagnosis, studies on the etiopathogenesis and genetics of the disease are the need of the hour for improving the survival rates. According to the Knudson hypothesis, also known as the two hit hypothesis, two hits on the retinoblastoma susceptibility (RB) gene is often considered as the initiating event in the development of the disease. Studies on the molecular basis of the disease have also led to deciphering the downstream events and thus in the discovery of biomarkers and related targeted therapies. Furthermore, improvements in molecular biology techniques enhanced the development of efficient methods for early diagnosis, genetic counseling, and prevention of the disease. In this review, we discuss the genetic and molecular features of retinoblastoma with a special emphasis on the mutation leading to the dysregulation of key signaling pathways involved in cell proliferation, DNA repair, and cellular plasticity. Also, we describe the classification, clinical and epidemiological relevance of the disease, with an emphasis on both the traditional and innovative treatments to tackle retinoblastoma. -y-wSoSY3DLWKHAp-w4afq Video Abstract [ABSTRACT FROM AUTHOR]

On average, there are about 300,000 new cases of brain cancer each year. Studies have shown that brain and central nervous system tumors are among the top ten causes of death. Due to the extent of this problem and the percentage of patients suffering from brain tumors, innovative therapeutic treatment methods are constantly being sought. One such innovative therapeutic method is photodynamic therapy (PDT). Photodynamic therapy is an alternative and unique technique widely used in dermatology and other fields of medicine for the treatment of oncological and nononcological lesions. Photodynamic therapy consists of the destruction of cancer cells and inducing inflammatory changes by using laser light of a specific wavelength in combination with the application of a photosensitizer. The most commonly used photosensitizers include 5-aminolevulinic acid for the enzymatic generation of protoporphyrin IX, Temoporfin—THPC, Photofrin, Hypericin and Talaporfin. This paper reviews the photosensitizers commonly used in photodynamic therapy for brain tumors. An overview of all three generations of photosensitizers is presented. Along with an indication of the limitations of the treatment of brain tumors, intraoperative photodynamic therapy and its possibilities are described as an alternative therapeutic method. [ABSTRACT FROM AUTHOR]

Introduction: Capmatinib is a mesenchymal-epithelial transition (MET) inhibitor authorized for metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutation treatment in adult patients. Case report: We report a case of an elderly female with a diagnosis of metastatic NSCLC with MET exon 14 skipping mutation who developed a severe hepatotoxicity after 7 weeks under treatment with capmatinib. Management & Outcome: Capmatinib was immediately discontinued. Hepatotoxicity is included as "warning and precautions" in the product information sheet. The patient was admitted with severe acute hepatitis, secondary hypocoagulability and acute deterioration of renal function. She experienced a rapid worsening with a fatal outcome three days after admission. The causal relationship between capmatinib and the appearance of hepatotoxicity was determined as probable according to Naranjo's modified Karch and Lasagna's imputability algorithm. Discussion: The recognition and diagnosis of drug-induced liver injury (DILI) are often difficult and delayed. Molecularly targeted agents require careful assessment of liver function both prior to and during therapy. Capmatinib hepatotoxicity is an infrequent but severe adverse drug reaction (ADR). Prescribing information includes recommendations about liver function monitoring. The main approachment for DILI is the removal of the causative agent. Detection and communication of ADRs to the Pharmacovigilance Systems have special relevance for novel drugs, with little data in real life setting. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and improved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated. Methods: We conducted a retrospective analysis of all patients, aged ≥18 years with histologically confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP). Results: Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly BRCA1 or BRCA2 (5 (18%)), HER2 (5 (18%)), MTAP (5 (18%)), and FGFR (3 (11%)). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs (n = 12 (11.8%)), 14 months in patients with actionable GAs treated with standard therapies (n = 17 (16.7%)), and 17 months in patients without actionable GAs treated with standard therapies (n = 73 (71.5%); p = 0.26). The absence of liver metastases was associated with better OS (HR = 0.471, p = 0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib. Interpretation: Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome. [ABSTRACT FROM AUTHOR]

Objective: Many patients with cholangiocarcinoma (CCA) are not surgical candidates, and the survival benefit of chemotherapy is less than 12 months. Several mutations and mutational clusters have recently been identified in CCA, some of which are pharmacologically targetable. The emergence of targeted therapies has significantly altered the treatment landscape of CCA and improved the prognosis for advanced or metastatic CCA. The purpose of this review is to describe past and current treatment strategies of CCA with a focus on FDA-approved targeted therapies. Data sources: A systematic evaluation of all FDA-approved targeted treatments for CCA through October 2022 was conducted. Information related to pharmacology, clinical efficacy, and safety was gathered from the package insert, and clinical trial data. Data summary: As of the writing of this review, four targeted agents are FDA approved for the treatment of locally advanced or metastatic CCA. These agents include the IDH1 inhibitor ivosidenib and the FGFR2 inhibitors pemigatinib, infigratinib, and futibatinib. Collectively, these agents have provided additional treatment options for select patients with previously treated locally advanced or unresectable CCA. These agents have also contributed to the development of other targeted therapies for the treatment of CCA and have opened the door for the exploration of novel treatment combinations such as chemotherapy and immunotherapy, which have recently become a front-line treatment option. Conclusions: Four targeted small molecule agents have emerged as effective therapies in the second-line setting for CCA, which has immensely changed the treatment landscape and directly led to further investigation of targeted agents and immunotherapy as treatment for CCA. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent studies have highlighted the importance of molecular targeted therapies in metastatic castration-resistant prostate cancer. These therapies, which aim to block specific molecules and related pathways in cancer cells, or in cells present in their microenvironment, and inhibit their proliferation, invasiveness and migration, while minimizing damage to healthy tissues, can be distinguished into four main categories: Prostate-Specific Membrane Antigen-targeted radionuclide therapies; DNA repair inhibitors; therapies targeting tumor neovascularization; and immune checkpoint inhibitors. The purpose of this review is to illustrate the characteristics, efficacy and limitations, of these therapies, some of which are already approved for clinical use while others are in clinical trials or at the pre-clinical stage of development, and to explore future research perspectives. Different solutions, from combined treatment with traditional drugs, to the use of nanomedicine for the selective release at the the tumor site, will be discussed, in order to improve their tolerability and therapeutic efficacy. Prostate cancer is the most frequent malignant tumor in men, and, despite the great improvements in survival in patients with localized cancer, the prognosis for metastatic disease remains poor. Novel molecular targeted therapies, which block specific molecules or signaling pathways in tumor cells or in their microenvironment, have shown encouraging results in metastatic castration-resistant prostate cancer. Among these therapeutic approaches, prostate-specific membrane antigen-targeted radionuclide therapies and DNA repair inhibitors represent the most promising ones, with some therapeutic protocols already approved by the FDA, whereas therapies targeting tumor neovascularization and immune checkpoint inhibitors have not yet demonstrated clear clinical benefits. In this review, the most relevant studies and clinical trials on this topic are illustrated and discussed, together with future research directions and challenges. [ABSTRACT FROM AUTHOR]

Targeted therapies have revolutionized the treatment for many patients with non-small cell lung cancer (NSCLC). Multiple new oral targeted therapies have been approved in the last decade; however, their overall efficacy may be reduced by poor adherence, treatment interruptions, or dose reductions due to adverse events. Most institutions lack standard monitoring protocols for toxicities from these targeted agents. This review describes important adverse events observed in clinical trials and reported by the U.S. Food and Drug Administration for both currently approved and upcoming promising therapies in the treatment of NSCLC. These agents cause a range of toxicities, including dermatologic, gastroenteric, pulmonary, and cardiac toxicities. This review proposes protocols for routine monitoring of these adverse events, both prior to initiation of therapy and while on treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To review the current state of molecular and genetic profiling of acute myeloid leukemia (AML) and its implications. DATA SOURCE: Peer-reviewed journal articles. CONCLUSION: Significant advances in the understanding of the pathology of acute myeloid leukemia have led to refined risk stratification of patients and application of novel targeted therapies based on genetic profiles. Minimal residual disease testing allows for highly sensitive disease surveillance that can be used to predict relapse and assess treatment response. IMPLICATIONS FOR NURSING PRACTICE: Accurate prognostication and therapeutic decision-making for patients with acute myeloid leukemia is dependent on molecular profiling. Being knowledgeable of the implications of minimal residual disease testing is critical for patient-centered care.

Cutaneo us vasculitis (CV) has a broad spectrum of etiologies, and drugs are one of the main culprits. With the increasing use of targeted therapies in medicine, especially in rheumatology and oncology, the number of CV cases reported due to these drugs has increased. Therefore, the recognition and treatment of CV associated with targeted agents have become more and more important. In the literature, anti-TNFs (n = 73, 59.5%), secukinumab (n = 7, 6%), rituximab (n = 5, 4%), tocilizumab (n = 1, 0.8%), ustekinumab (n = 8, 6.5%), abatacept (n = 3, 2.4%), Janus kinase inhibitors (n = 3, 2.4%), alemtuzumab (n = 3, 2.4%), and immune checkpoint inhibitors (n = 20, 16%) have been reported as responsible agents. However, our knowledge of the pathogenetic mechanisms is fairly limited, and the standardized management is yet to be established. Furthermore, though it is uncommon, this complication may pose a safety issue. In this manuscript, we reviewed the literature on CV with or without systemic involvement related to targeted agents. We also proposed the pathogenetic mechanisms of these adverse events. Thus, we aimed to make it easier for clinicians to manage similar cases by reviewing the diagnosis and treatment processes. Key Points • It should be kept in mind that targeted therapies can lead to CV with or without systemic signs, which sometimes withholds their uses. • Since targeted therapies are often used in the treatment of autoimmune and inflammatory diseases, CV associated with targeted therapies is difficult to recognize, and it is often mistakenly attributed to the underlying disease. • Although the pathogenesis of CV associated with targeted therapies is not fully understood, there are several proposed mechanisms. • Corticosteroids are the mainstay of treatment after discontinuation of the offending targeted agent. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer in young adults spans all ethnic backgrounds and is associated with advanced disease and poor outcomes. Identification of genetic changes that are associated with disease and can subsequently be targeted with specific therapies is associated with improved survival. As such, comprehensive molecular testing is recommended in all advanced young adults with non-small cell lung cancer. (1) Background: Non-small cell lung cancer (NSCLC) in young patients is uncommon. Real-world evidence on the outcomes of these patients is limited. (2) Methods: We conducted a retrospective cohort study of young NSCLC patients, age < 50 years at diagnosis, who were treated between 2011–2020 in South-East-London cancer centres. Clinicopathological characteristics, treatment and outcomes were analysed. (3) Results: Of 248 NSCLC patients, median age was 46 years, 50% (n = 125) female, 58% (n = 145) white, 18% (n = 45) black and 4% (n = 10) Asian ethnicity. Amongst patients with a documented smoking history, 30% (n = 64) were never-smokers. Most patients had adenocarcinoma (77%, n = 191) and presented with metastatic disease (67%, n = 166). Only 31% (n = 76) had treatment with curative intent. In patients who presented or developed metastatic non-squamous NSCLC (n = 179), EGFR mutation status was known in 88% (n = 157) and mutation present in 19% (n = 34), ALK was known in 66% (n = 118) with a translocation in 10% (n = 18), ROS1 status was known in 57% (n = 102) with a translocation in 4% (n = 8), and KRAS status was known in 66% (n = 119) with a mutation in 12% (n = 22). Overall, 76% (n = 152) patients with metastatic NSCLC received first-line systemic anti-cancer therapy. Median overall survival in metastatic NSCLC was 9.0 months (95% CI 6.5–11.6 months), with superior median overall survival in those with a targeted therapy option (28.7 months) compared to those without (6.6 months; p < 0.001). (4) Conclusion: Young patients contribute a significant proportion of those presenting with lung cancer. They present with advanced stage at diagnosis and have a poor prognosis. Identification of a targeted therapy option is associated with improved survival. However, most patients do not have a known genomic driver, which is in part due to limited testing, particularly in the early years of this study period. These findings highlight the particular importance of rapid-turnaround comprehensive genomic profiling in this age group and the need to identify strategies to facilitate earlier diagnosis in young NSCLC patients. [ABSTRACT FROM AUTHOR]

With the development of molecular targeted therapies, a wide array of dermatologic toxicities is appearing. Their prevention, recognition, and management by dermatologists is critical to ensure antineoplastic treatment continuation. The objective of this study was to provide a literature review of the most common dermatologic toxicities due to targeted therapies in oncologic patients, including their clinical presentation, prevention, and management.

For a long time, mesenchymal stem cells (MSCs) were discussed only as stem cells which could give rise to different types of cells. However, when it became clear that their presence in the tumor microenvironment (TME) was like a green light for tumorigenesis, they emerged from the ashes. This review was arranged to provide a comprehensive and precise description of MSCs’ role in regulating tumorigenesis and to discuss the dark and the bright sides of cancer treatment strategies using MSCs.To gather the details about MSCs, we made an intensive literature review using keywords, including MSCs, tumor microenvironment, tumorigenesis, and targeted therapy. Through transferring cytokines, growth factors, and microRNAs, MSCs maintain the cancer stem cell population, increase angiogenesis, provide a facility for cancer metastasis, and shut down the anti-tumor activity of the immune system. Although MSCs progress tumorigenesis, there is a consensus that these cells could be used as a vehicle to transfer anti-cancer agents into the tumor milieu. This feature opened a new chapter in MSCs biology, this time from the therapeutic perspective. Although the data are not sufficient, the advent of new genetic engineering methods might make it possible to engage these cells as Trojan horses to eliminate the malignant population. So many years of investigation showed that MSCs are an important group of cells, residing in the TME, studying the function of which not only could add a delicate series of information to the process of tumorigenesis but also could revolutionize cancer treatment strategies.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC, some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and improved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated. Methods: We conducted a retrospective analysis of all patients, aged ≥18 years with histologically confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP). Results: Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly BRCA1 or BRCA2 (5 (18%)), HER2 (5 (18%)), MTAP (5 (18%)), and FGFR (3 (11%)). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs (n = 12 (11.8%)), 14 months in patients with actionable GAs treated with standard therapies (n = 17 (16.7%)), and 17 months in patients without actionable GAs treated with standard therapies (n = 73 (71.5%); p = 0.26). The absence of liver metastases was associated with better OS (HR = 0.471, p = 0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib. Interpretation: Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome.

On average, there are about 300,000 new cases of brain cancer each year. Studies have shown that brain and central nervous system tumors are among the top ten causes of death. Due to the extent of this problem and the percentage of patients suffering from brain tumors, innovative therapeutic treatment methods are constantly being sought. One such innovative therapeutic method is photodynamic therapy (PDT). Photodynamic therapy is an alternative and unique technique widely used in dermatology and other fields of medicine for the treatment of oncological and nononcological lesions. Photodynamic therapy consists of the destruction of cancer cells and inducing inflammatory changes by using laser light of a specific wavelength in combination with the application of a photosensitizer. The most commonly used photosensitizers include 5-aminolevulinic acid for the enzymatic generation of protoporphyrin IX, Temoporfin—THPC, Photofrin, Hypericin and Talaporfin. This paper reviews the photosensitizers commonly used in photodynamic therapy for brain tumors. An overview of all three generations of photosensitizers is presented. Along with an indication of the limitations of the treatment of brain tumors, intraoperative photodynamic therapy and its possibilities are described as an alternative therapeutic method.

Simple Summary: The NGS and other molecular techniques creates huge hopes for effective CUP patients treatment and to select them for molecularly targeted therapies (agnostic therapies) and immunotherapy. Development of diagnostic technologies and biologically targeted therapies could make CUP' patients access to modern therapies and change their outcome. Cancer of unknown primary (CUP) represents a rare oncological and heterogeneous disease in which one or more metastases are present, but the location of the primary site is unknown. Pathological diagnosis, using immunohistochemistry, of such metastatic materials is challenging and frequently does not allow for determining the tissue of origin (ToO). The selection of systemic therapy in patients with CUP is usually based on empiric grounds, and the prognosis is generally unfavourable. New molecular techniques could identify the tissue of origin and be used to select systemic agnostic therapies in various malignancies with specific molecular abnormalities. Targetable driver mutations or gene rearrangements in cancer cells may be identified using various molecular assays, of which particularly valuable are next-generation sequencing techniques. These assays may identify tumour sources and allow personalized treatments. However, current guidelines for CUP management do not recommend routine testing of gene expression and epigenetic factors. This is mainly due to the insufficient evidence supporting the improvement of CUP's prognosis by virtue of this approach. This review summarizes the advantages and disadvantages of new genetic techniques in CUP diagnostics and proposes updating the recommendations for CUP management. [ABSTRACT FROM AUTHOR]

Despite the recent development of precision medicine and targeted therapies, lung cancer remains the top cause of cancer-related mortality worldwide. The patients diagnosed with metastatic disease have a five-year survival rate lower than 6%. In metastatic disease, EGFR is the most common driver of mutation, with the most common co-driver hitting TP53. EGFR-positive patients are offered the frontline treatment with tyrosine kinase inhibitors, yet the development of resistance and the lack of alternative therapies make this group of patients only fit for clinical trial participation. Since mutant p53 is the most common co-driver in the metastatic setting, therapies reactivating the p53 pathway might serve as a promising alternative therapeutic approach in patients who have developed a resistance to tyrosine kinase inhibitors. This review focuses on the molecular background of EGFR-mutated lung cancer and discusses novel therapeutic options converging on the reactivation of p53 tumor suppressor pathways. [ABSTRACT FROM AUTHOR]

Abstract Pathogenic germline BRCA2 variants may be associated with an increased risk of hypopharyngeal squamous cell carcinoma that is more responsive to chemoradiation and chemotherapeutics targeting defective double‐strand DNA repair.

Background: Pancreatic adenocarcinoma is one of the most aggressive malignancies with extremely low survival rate. Studies have shown that the exploration of key genes can provide a basis for targeted treatment of these patients. The genomic architecture of the Pakistani pancreatic adenocarcinoma patients remains unexplored. Keeping the scenario in place, the current study aims to analyse 88 cancer related genes in Pakistani pancreatic adenocarcinoma patients in order to elucidate candidate gene(s) for targeted molecular therapy. Methods and results: A total 18 patients were included in the study initially and FFPE tumor samples were obtained. After confirmation of diagnosis and appropriate tumor content, DNA was extracted. Based on the quality and quantity of the extracted DNA, six pancreatic adenocarcinoma tumor samples were selected. Following to this, all the samples were subjected to targeted sequencing (Axen Cancer Panel 1). Variant detection was done and clinical significance of identified variants was assessed using ClinVar database. Targeted sequencing of tumor samples revealed a total of 29 alterations in the coding region of various genes. Among these five pathogenic variants were found in KRAS, BRCA1, TP53 and APC genes. Conclusion: This is the first study that explores genes involved in pancreatic adenocarcinoma from the Pakistani population. Results obtained from the pilot study can guide us about the key genetic players in the Pakistani pancreatic adenocarcinoma population. This can lead to our better understanding of the molecular targeted therapies for these patients and designing future researches on larger sample size. [ABSTRACT FROM AUTHOR]

Stage IV colorectal cancer treatment includes targeted therapy depending on RAS status. During disease progression, loss or gain of RAS mutations could happen, supporting the hypothesis of the evolutionary pressure of therapy. Circulating tumor DNA (ctDNA) are nucleic acids released to the bloodstream by the tumor during its development and may be detected by liquid biopsy. The Idylla© Biocartis, a fully automated real-time-PCR-based molecular diagnostic system, was used in a patient with metastatic colorectal cancer with a NRAS mutation in progression after several therapeutic lines. The ctDNA mutational analysis was performed and revealed the absence of mutations in the KRAS, NRAS, and BRAF genes. The patient started the third line of palliative chemotherapy with irinotecan + cetuximab and achieved a partial response for the first time. The authors describe a case in which liquid biopsy determined the higher progression-free survival achieved. [ABSTRACT FROM AUTHOR]

The role of imaging in cancer diagnosis and treatment has evolved at the same rapid pace as cancer management. Over the last twenty years, with the advancement of technology, oncology has become a multidisciplinary field that allows for researchers and clinicians not only to create individualized treatment options for cancer patients, but also to evaluate patients’ response to therapy with increasing precision. Familiarity with these concepts is a requisite for current and future radiologists, as cancer imaging studies represent a significant and growing component of any radiology practice, from tertiary cancer centers to community hospitals.In this review we provide the framework to teach cancer imaging in the era of genomic oncology. After reading this article, readers should be able to illustrate the basics cancer genomics, modern cancer genomics, to summarize the types of systemic oncologic therapies available, their patterns of response and their adverse events, to discuss the role of imaging in oncologic clinical trials and the role of tumor response criteria and to display the future directions of oncologic imaging.

Thyroid carcinoma of follicular cell origin exists on a histopathologic and clinical spectrum. The authors focus on the category of tumors that fall between the very favorable well-differentiated thyroid carcinomas and the very unfavorable anaplastic thyroid carcinomas. These intermediately aggressive tumors include poorly differentiated thyroid carcinoma and the newly defined differentiated high-grade thyroid carcinoma. Both diagnoses require certain histopathologic requirements be met in order to accurately identify these tumors post-operatively. Management remains primarily surgical though adjunctive treatments such as molecular targeted therapies (eg, tyrosine kinase inhibitors) and differentiation therapy (to restore tumor response to radioactive iodine) are also becoming available., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

For a long time, mesenchymal stem cells (MSCs) were discussed only as stem cells which could give rise to different types of cells. However, when it became clear that their presence in the tumor microenvironment (TME) was like a green light for tumorigenesis, they emerged from the ashes. This review was arranged to provide a comprehensive and precise description of MSCs’ role in regulating tumorigenesis and to discuss the dark and the bright sides of cancer treatment strategies using MSCs. To gather the details about MSCs, we made an intensive literature review using keywords, including MSCs, tumor microenvironment, tumorigenesis, and targeted therapy. Through transferring cytokines, growth factors, and microRNAs, MSCs maintain the cancer stem cell population, increase angiogenesis, provide a facility for cancer metastasis, and shut down the anti-tumor activity of the immune system. Although MSCs progress tumorigenesis, there is a consensus that these cells could be used as a vehicle to transfer anti-cancer agents into the tumor milieu. This feature opened a new chapter in MSCs biology, this time from the therapeutic perspective. Although the data are not sufficient, the advent of new genetic engineering methods might make it possible to engage these cells as Trojan horses to eliminate the malignant population. So many years of investigation showed that MSCs are an important group of cells, residing in the TME, studying the function of which not only could add a delicate series of information to the process of tumorigenesis but also could revolutionize cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Hemorrhage in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) may be attributed to chemotherapy and local tumor irradiation. Evidence of the relationship between hemorrhage in R/M HNSCC and targeted therapies, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors, or immune checkpoint inhibitors, is limited. We aimed to identify epidemiological and clinical data related to the occurrence of hemorrhage in R/M HNSCC and to explore its relationship with various therapies. We describe information obtained from literature searches as well as data extracted from a commercial database and a database from the author's institution (Istituto Nazionale dei Tumori of Milan). Evidence suggests that most bleeding events in R/M HNSCC are minor. Clinical trial safety data do not identify a causal association between hemorrhage and anti‐EGFR agents or immune checkpoint inhibitors. In contrast, anti‐VEGF agents are associated with increased, and often severe/fatal, hemorrhagic complications. [ABSTRACT FROM AUTHOR]

Context: Radioiodine-refractory thyroid cancers have poor outcomes and limited therapeutic options (tyrosine kinase inhibitors) due to transient efficacy and toxicity of treatments. Therefore, combinatorial treatments with new therapeutic approaches are needed. Many studies link G protein-coupled receptors (GPCRs) to cancer cell biology.Objective: To perform a specific atlas of GPCR expression in progressive and refractory thyroid cancer to identify potential targets among GPCRs aiming at drug repositioning.Methods: We analyzed samples from tumor and normal thyroid tissues from 17 patients with refractory thyroid cancer (12 papillary thyroid cancers [PTCs] and 5 follicular thyroid cancers [FTCs]). We assessed GPCR mRNA expression using NanoString technology with a custom panel of 371 GPCRs. The data were compared with public repositories and pharmacological databases to identify eligible drugs. The analysis of prognostic value of genes was also performed with TCGA datasets.Results: With our transcriptomic analysis, 4 receptors were found to be downregulated in FTC (VIPR1, ADGRL2/LPHN2, ADGRA3, and ADGRV1). In PTC, 24 receptors were deregulated, 7 of which were also identified by bioinformatics analyses of publicly available datasets on primary thyroid cancers (VIPR1, ADORA1, GPRC5B, P2RY8, GABBR2, CYSLTR2, and LPAR5). Among all the differentially expressed genes, 22 GPCRs are the target of approved drugs and some GPCRs are also associated with prognostic factors.Discussion: For the first time, we performed GPCR mRNA expression profiling in progressive and refractory thyroid cancers. These findings provide an opportunity to identify potential therapeutic targets for drug repositioning and precision medicine in radioiodine-refractory thyroid cancer. [ABSTRACT FROM AUTHOR]

Pathogenic germline BRCA2 variants may be associated with an increased risk of hypopharyngeal squamous cell carcinoma that is more responsive to chemoradiation and chemotherapeutics targeting defective double‐strand DNA repair. [ABSTRACT FROM AUTHOR]

Pharmacometric methods have hugely benefited from progress in analytical and computer sciences during the past decades, and play nowadays a central role in the clinical development of new medicinal drugs. It is time that these methods translate into patient care through therapeutic drug monitoring (TDM), due to become a mainstay of precision medicine no less than genomic approaches to control variability in drug response and improve the efficacy and safety of treatments. In this review, we make the case for structuring TDM development along five generic questions: 1) Is the concerned drug a candidate to TDM? 2) What is the normal range for the drug's concentration? 3) What is the therapeutic target for the drug's concentration? 4) How to adjust the dosage of the drug to drive concentrations close to target? 5) Does evidence support the usefulness of TDM for this drug? We exemplify this approach through an overview of our development of the TDM of imatinib, the very first targeted anticancer agent. We express our position that a similar story shall apply to other drugs in this class, as well as to a wide range of treatments critical for the control of various life-threatening conditions. Despite hurdles that still jeopardize progress in TDM, there is no doubt that upcoming technological advances will shape and foster many innovative therapeutic monitoring methods.

Pharmacometric methods have hugely benefited from progress in analytical and computer sciences during the past decades, and play nowadays a central role in the clinical development of new medicinal drugs. It is time that these methods translate into patient care through therapeutic drug monitoring (TDM), due to become a mainstay of precision medicine no less than genomic approaches to control variability in drug response and improve the efficacy and safety of treatments. In this review, we make the case for structuring TDM development along five generic questions: 1) Is the concerned drug a candidate to TDM? 2) What is the normal range for the drug's concentration? 3) What is the therapeutic target for the drug's concentration? 4) How to adjust the dosage of the drug to drive concentrations close to target? 5) Does evidence support the usefulness of TDM for this drug? We exemplify this approach through an overview of our development of the TDM of imatinib, the very first targeted anticancer agent. We express our position that a similar story shall apply to other drugs in this class, as well as to a wide range of treatments critical for the control of various life-threatening conditions. Despite hurdles that still jeopardize progress in TDM, there is no doubt that upcoming technological advances will shape and foster many innovative therapeutic monitoring methods. [ABSTRACT FROM AUTHOR]

The goal of all medical activity is to preserve health in fit people, and to restore the sick into a state of complete physical, mental and social wellbeing. In an effort to determine whether we are achieving this last goal in oncology, herein we review the biological and clinical framework that has led to the foundations of the current anti-cancer treatment paradigm.Currently, cancer therapy is still based on the ancient axiom that states that the complete eradication of the tumor burden is the only way to achieve a cure. This strategy has led to a substantial improvement in survival rates as cancer mortality rates have dropped in an unprecedented way. Despite this progress, more than 9 million people still die from cancer every year, indicating that the current treatment strategy is not leading to a cancer cure, but to a cancer remission, that is “the temporary absence of manifestations of a particular disease”; after months or years of remission, in most patients, cancer will inevitably recur. Our critical analysis indicates that it is time to discuss about the new key challenges and future directions in clinical oncology. We need to generate novel treatment strategies more suited to the current clinical reality. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumors are mesenchymal lesions that arise at a variety of sites, most commonly the pleura. Thoracic forms are generally asymptomatic at the time of diagnosis, and the radiographic features are a well-circumscribed, peripheral mass that abuts the pleural surface, frequently attached by a pedicle. Solitary fibrous tumors are mesenchymal lesions that arise at a variety of sites, most commonly the pleura. Most patients are asymptomatic at diagnosis, with lesions being detected incidentally. Nevertheless, some patients present due to symptoms from local tumor compression (eg. of the airways and pulmonary parenchyma). Furthermore, radiological methods are not always conclusive in making a diagnosis, and thus, pathological analysis is often required. In the past three decades, immunohistochemical techniques have provided a gold standard in solitary fibrous tumor diagnosis. The signature marker of solitary fibrous tumor is the presence of the NAB2-STAT6 fusion that can be reliably detected with a STAT6 antibody. While solitary fibrous tumors are most often benign, they can be malignant in 10-20% of the cases. Unfortunately, histological parameters are not always predictive of benign vs malignant solitary fibrous tumors. As solitary fibrous tumors are generally regarded as relatively chemoresistant tumors; treatment is often limited to localized treatment modalities. The optimal treatment of solitary fibrous tumors appears to be complete surgical resection for both primary and local recurrent disease. However, in cases of suboptimal resection, large disease burden, or advanced recurrence, a multidisciplinary approach may be preferable. Specifically, radiotherapy for inoperable local disease can provide palliation/shrinkage. Given their sometimes -unpredictable and often- protracted clinical course, long-term follow-up post-resection is recommended

Clinical practice guidelines for the management of cholangiocarcinoma (CCA)/biliary tract cancer recommend genomic profiling to guide treatment decisions. Variable access to such profiling across Italy means many oncologists are unfamiliar with when and how to conduct genetic testing and prescribe targeted treatments. A Scientific Board of Italian oncologists who treat CCA (the authors) developed recommendations, based on recent clinical evidence, for using molecular testing in diagnosing, assessing, and treating CCA in Italy. The Delphi process was used to reach consensus on these recommendations among 38 Italian oncologists. Consensus was considered to be met if ≥ 66.7 % of the panel agreed or strongly agreed with each statement. Consensus was reached on 28 statements across four themes: (1) epidemiology and risk factors; (2) diagnosis, including molecular diagnosis; (3) treatment selection; and (4) treatment safety. These recommendations should aid Italian clinicians in selecting appropriate treatment options for their patients. [Display omitted] • Familiarity with genomic profiling for CCA varies in Italian oncologists. • Next-generation sequencing should be used for profiling at diagnosis in CCA. • Cisplatin+gemcitabine+durvalumab is considered a 1st-line therapy for advanced CCA. • Targetable gene alterations should guide 2nd-line therapy; if absent, use FOLFOX. • Ocular and cardiac toxicities should be monitored if using FGFR2 or IDH1 inhibitors. [ABSTRACT FROM AUTHOR]

Pravinkumar Vishwanath Ingle, Sarah Zakiah Samsudin, Pei Qi Chan, Mei Kei Ng, Li Xuan Heng, Siu Ching Yap, Amy Siaw Hui Chai, Audrey San Ying WongDepartment of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, MalaysiaAbstract: This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for hepatocellular carcinoma (HCC). As HCC is the third most common cause of cancer-related death worldwide, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed and developing world. Over the past 15 years, the incidence of HCC has more than doubled and it increases with advancing age. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcohol abuse, tobacco smoking, and metabolic syndrome (including obesity, diabetes, and fatty liver disease). Treatment options have improved in the past few years, particularly with the approval of several molecular-targeted therapies. The researchers are actively pursuing novel therapeutic targets as well as predictive biomarker for treatment of HCC. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics. Nevertheless, there are many emerging agents still under clinical trials and yet to show promising results. Hence, future therapeutic options may include different combination of novel therapeutic interventions.Keywords: hepatocellular carcinoma, HCC, novel therapeutics, treatment, management, molecular targeted therapies, clinical drug trial

Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades. Especially for patients with intermediate or high-risk AML, which often show relapse. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the best chance for cure. Here we review the state of the art therapy of AML, with special focus on new developments in immunotherapies and cellular therapies including HSCT and particularly discuss the impact of new conditioning and haplo-identical donor regimens for HSCT, post-transplant strategies for preventing and treating relapse, and emerging novel therapeutic options.