Pub Date : 2024-12-25DOI: 10.1016/j.critrevonc.2024.104607
Lorenza Di Marco , Adriana Romanzi , Alessandra Pivetti , Nicola De Maria , Federico Ravaioli , Massimiliano Salati , Erica Villa , Fabrizio Di Benedetto , Paolo Magistri , Massimo Dominici , Antonio Colecchia , Stefano Di Sandro , Andrea Spallanzani
Liver transplantation (LT) is a curative strategy for hepatocellular carcinoma (HCC), but the risk of HCC recurrence remains a challenging problem. In patients with HCC recurrence after LT (HCC-R_LT), the locoregional and surgical approaches are complex, and the guidelines do not report evidence-based strategies for the management of immunosuppression. In recent years, immunotherapy has become an effective option for patients with advanced HCC in pre-transplant settings. However, due to the risk of potentially fatal allograft rejection, the use of immunotherapy is avoided in post-transplant settings. Combining immunosuppressants with immunotherapy in transplant patients is also challenging due to the complex tumor microenvironment and immunoreactivity. The fear of acute liver rejection and the lack of predictive factors hinder the successful clinical application of immunotherapy for post-liver transplantation HCC recurrence. This review aims to comprehensively summarize the risk of HCC-R_LT, the available evidence for the efficacy of immunotherapy in patients with HCC-R_LT, and the clinical issues regarding the innovative management of this patient population.
{"title":"Suppressing, stimulating and/or inhibiting: The evolving management of HCC patient after liver transplantation","authors":"Lorenza Di Marco , Adriana Romanzi , Alessandra Pivetti , Nicola De Maria , Federico Ravaioli , Massimiliano Salati , Erica Villa , Fabrizio Di Benedetto , Paolo Magistri , Massimo Dominici , Antonio Colecchia , Stefano Di Sandro , Andrea Spallanzani","doi":"10.1016/j.critrevonc.2024.104607","DOIUrl":"10.1016/j.critrevonc.2024.104607","url":null,"abstract":"<div><div>Liver transplantation (LT) is a curative strategy for hepatocellular carcinoma (HCC), but the risk of HCC recurrence remains a challenging problem. In patients with HCC recurrence after LT (HCC-R_LT), the locoregional and surgical approaches are complex, and the guidelines do not report evidence-based strategies for the management of immunosuppression. In recent years, immunotherapy has become an effective option for patients with advanced HCC in pre-transplant settings. However, due to the risk of potentially fatal allograft rejection, the use of immunotherapy is avoided in post-transplant settings. Combining immunosuppressants with immunotherapy in transplant patients is also challenging due to the complex tumor microenvironment and immunoreactivity. The fear of acute liver rejection and the lack of predictive factors hinder the successful clinical application of immunotherapy for post-liver transplantation HCC recurrence. This review aims to comprehensively summarize the risk of HCC-R_LT, the available evidence for the efficacy of immunotherapy in patients with HCC-R_LT, and the clinical issues regarding the innovative management of this patient population.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"207 ","pages":"Article 104607"},"PeriodicalIF":5.5,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-18DOI: 10.1016/j.critrevonc.2024.104601
Bishma Jayathilaka , Farah Mian , Jo Cockwill , Fanny Franchini , George Au-Yeung , Maarten IJzerman
Background
Immune-related adverse events (irAE) pose challenges to the use of immune checkpoint inhibitors (ICI). While risk factors for irAE are emerging, most studies are small, retrospective analyses that seldom report on diverse cancers or rare irAE. This paper reports a systematic review that summarises literature on irAE risk factors across cancers and proposes a categorisation approach.
Method
A systematic search was conducted in Medline OVID, Embase and Web of Science databases following PRISMA guidelines (CRD42022310127). Original research published in peer-reviewed journals between January 2017-Decmeber 2021 were selected. Eligible studies included patients with any cancer and evaluated any potential risk factor for any grade/type of irAE. Study design, sample size, and method for analysing association between irAE and risk factors were compared.
Results
A total of 293 eligible studies containing 305,879 patients receiving ICI reported irAE in 58,291 patients (19.1 %). There were 221 retrospective, 55 prospective studies, and 17 systematic reviews/meta-analyses. Eighteen studies evaluated the predictive validity of models. Proposed risk factors were grouped based on common themes and underlying aetiology: 1) patient, 2) laboratory, 3) medical history, 4) cancer-related, 5) clinical score, 6) medications, and 7) imaging features. Opposing associations were reported between advancing age and irAE risk.
Conclusion
This systematic review provides a comprehensive overview of evidence on irAE risk factors across a large patient population. Studies were heterogeneous resulting from variations in design, sample size and analysis method, and lack generalisability due to statistically underpowered evidence. We propose an approach to categorise potential irAE risk factors to support ongoing collaborative research.
背景：免疫相关不良事件（irAE）对免疫检查点抑制剂（ICI）的使用提出了挑战。虽然irAE的危险因素正在出现，但大多数研究都是小规模的回顾性分析，很少报道不同的癌症或更罕见的irAE。本文报道了一项系统综述，总结了有关癌症中irAE风险因素的文献，并提出了一种分类方法。方法：按照PRISMA指南（CRD42022310127）系统检索Medline OVID、Embase和Web of Science数据库。选取2017年1月至2021年12月在同行评议期刊上发表的原创研究。符合条件的研究包括任何癌症患者，并评估任何级别/类型的irAE的任何潜在危险因素。比较研究设计、样本量和分析irAE与危险因素之间关系的方法。结果：共有293项符合条件的研究，包括305,879例接受ICI的患者，在58,291例独特患者（19.1%）中报告了irAE。共有221项回顾性研究、55项前瞻性研究和17项系统综述/荟萃分析。18项研究评估了模型的预测有效性。建议的危险因素根据共同的主题和潜在的病因进行分组：1)患者，2)实验室，3)病史，4)癌症相关，5)临床评分，6)药物，7)影像学特征。据报道，年龄增长与irAE风险之间存在相反的关联。结论：本系统综述对大量患者群体中irAE危险因素的证据进行了全面总结。由于设计、样本量和分析方法的差异，研究具有异质性，并且由于统计证据不足而缺乏通用性。我们提出了一种对潜在风险因素进行分类的方法，以支持正在进行的合作研究。
{"title":"Analysis of risk factors for immune-related adverse events induced by immune checkpoint inhibitor treatment in cancer: A comprehensive systematic review","authors":"Bishma Jayathilaka , Farah Mian , Jo Cockwill , Fanny Franchini , George Au-Yeung , Maarten IJzerman","doi":"10.1016/j.critrevonc.2024.104601","DOIUrl":"10.1016/j.critrevonc.2024.104601","url":null,"abstract":"<div><h3>Background</h3><div>Immune-related adverse events (irAE) pose challenges to the use of immune checkpoint inhibitors (ICI). While risk factors for irAE are emerging, most studies are small, retrospective analyses that seldom report on diverse cancers or rare irAE. This paper reports a systematic review that summarises literature on irAE risk factors across cancers and proposes a categorisation approach.</div></div><div><h3>Method</h3><div>A systematic search was conducted in Medline OVID, Embase and Web of Science databases following PRISMA guidelines (CRD42022310127). Original research published in peer-reviewed journals between January 2017-Decmeber 2021 were selected. Eligible studies included patients with any cancer and evaluated any potential risk factor for any grade/type of irAE. Study design, sample size, and method for analysing association between irAE and risk factors were compared.</div></div><div><h3>Results</h3><div>A total of 293 eligible studies containing 305,879 patients receiving ICI reported irAE in 58,291 patients (19.1 %). There were 221 retrospective, 55 prospective studies, and 17 systematic reviews/meta-analyses. Eighteen studies evaluated the predictive validity of models. Proposed risk factors were grouped based on common themes and underlying aetiology: 1) patient, 2) laboratory, 3) medical history, 4) cancer-related, 5) clinical score, 6) medications, and 7) imaging features. Opposing associations were reported between advancing age and irAE risk.</div></div><div><h3>Conclusion</h3><div>This systematic review provides a comprehensive overview of evidence on irAE risk factors across a large patient population. Studies were heterogeneous resulting from variations in design, sample size and analysis method, and lack generalisability due to statistically underpowered evidence. We propose an approach to categorise potential irAE risk factors to support ongoing collaborative research.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"207 ","pages":"Article 104601"},"PeriodicalIF":5.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.critrevonc.2024.104521
Mario Occhipinti , Marta Brambilla , Raimondo Di Liello , Paolo Ambrosini , Lorenzo Lobianco , Rita Leporati , Maria Salvarezza , Fabiana Vitiello , Silvia Marchesi , Sara Manglaviti , Teresa Beninato , Laura Mazzeo , Claudia Proto , Arsela Prelaj , Roberto Ferrara , Carminia Maria Della Corte , Giuseppe Lo Russo , Filippo de Braud , Monica Ganzinelli , Giuseppe Viscardi
{"title":"Erratum to “Unleashing precision: A review of targeted approaches in pleural mesothelioma” [Crit. Rev. Oncol./Hematol. 203C (2024) 104481]","authors":"Mario Occhipinti , Marta Brambilla , Raimondo Di Liello , Paolo Ambrosini , Lorenzo Lobianco , Rita Leporati , Maria Salvarezza , Fabiana Vitiello , Silvia Marchesi , Sara Manglaviti , Teresa Beninato , Laura Mazzeo , Claudia Proto , Arsela Prelaj , Roberto Ferrara , Carminia Maria Della Corte , Giuseppe Lo Russo , Filippo de Braud , Monica Ganzinelli , Giuseppe Viscardi","doi":"10.1016/j.critrevonc.2024.104521","DOIUrl":"10.1016/j.critrevonc.2024.104521","url":null,"abstract":"","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104521"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to “Prevalence of treatment-related adverse events (TRAEs) with antibody-drug conjugates in metastatic breast cancer patients: A systematic review and meta-analysis” [Crit. Rev. Oncol./Hematol. 204 (2024) 104527]","authors":"Silvia Belloni , Paola Tiberio , Rita De Sanctis , Arianna Magon , Armando Santoro , Alberto Zambelli , Rosario Caruso , Cristina Arrigoni","doi":"10.1016/j.critrevonc.2024.104550","DOIUrl":"10.1016/j.critrevonc.2024.104550","url":null,"abstract":"","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104550"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.critrevonc.2024.104530
Lorenzo Antonuzzo
{"title":"Corrigendum to “The emerging HER2 landscape in Colorectal Cancer: The key to unveil the future treatment algorithm?” [Crit. Rev. Oncol./Hematol. 204 (2024) 104515]","authors":"Lorenzo Antonuzzo","doi":"10.1016/j.critrevonc.2024.104530","DOIUrl":"10.1016/j.critrevonc.2024.104530","url":null,"abstract":"","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104530"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.critrevonc.2024.104542
M. Sirico , F. Jacobs , C. Molinelli , Guilherme Nader-Marta , V. Debien , H.Faith Dewhurst , M. Pallesch , F. Merloni , C. Gianni , U. De Giorgi , Evandro de Azambuja
{"title":"Corrigendum to “Navigating the complexity of PI3K/AKT pathway in HER-2 negative breast cancer: Biomarkers and beyond” [Crit. Rev. Oncol./Hematol. 200C (2024) 104404]","authors":"M. Sirico , F. Jacobs , C. Molinelli , Guilherme Nader-Marta , V. Debien , H.Faith Dewhurst , M. Pallesch , F. Merloni , C. Gianni , U. De Giorgi , Evandro de Azambuja","doi":"10.1016/j.critrevonc.2024.104542","DOIUrl":"10.1016/j.critrevonc.2024.104542","url":null,"abstract":"","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104542"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The advent of immune checkpoint inhibitors (ICIs) has deeply reshaped the therapeutic algorithm of triple-negative breast cancer (TNBC). However, there is considerable scope for better engagement of the immune system in other BC subtypes. ICIs have paved the way for investigations into emerging immunotherapeutic strategies, such as immune cell engagers (ICEs) that work by promoting efficient tumor cell killing through the redirection of immune system against cancer cells. Most ICEs are bispecific antibodies that simultaneously recognize and bind to both cancer and immune cells generating an artificial synapse. Major side effects are cytokine release syndrome, hepatotoxicity, and neurotoxicity related to inappropriate immune system activation. Here, we provide a comprehensive overview of this compounds, the available preclinical and clinical evidence supporting their investigation and development in BC also highlighting the challenges that have prevented their widespread use in oncology. Finally, major strategies are explored to broaden their use in BC.
{"title":"Warming-up the immune cell engagers (ICEs) era in breast cancer: state of the art and future directions","authors":"Aldo Caltavituro , Roberto Buonaiuto , Fabio Salomone , Giovanna Pecoraro , Federica Martorana , Vincenzo Di Lauro , Giacomo Barchiesi , Fabio Puglisi , Lucia Del Mastro , Filippo Montemurro , Mario Giuliano , Grazia Arpino , Michelino De Laurentiis","doi":"10.1016/j.critrevonc.2024.104577","DOIUrl":"10.1016/j.critrevonc.2024.104577","url":null,"abstract":"<div><div>The advent of immune checkpoint inhibitors (ICIs) has deeply reshaped the therapeutic algorithm of triple-negative breast cancer (TNBC). However, there is considerable scope for better engagement of the immune system in other BC subtypes. ICIs have paved the way for investigations into emerging immunotherapeutic strategies, such as immune cell engagers (ICEs) that work by promoting efficient tumor cell killing through the redirection of immune system against cancer cells. Most ICEs are bispecific antibodies that simultaneously recognize and bind to both cancer and immune cells generating an artificial synapse. Major side effects are cytokine release syndrome, hepatotoxicity, and neurotoxicity related to inappropriate immune system activation. Here, we provide a comprehensive overview of this compounds, the available preclinical and clinical evidence supporting their investigation and development in BC also highlighting the challenges that have prevented their widespread use in oncology. Finally, major strategies are explored to broaden their use in BC.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104577"},"PeriodicalIF":5.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent advancements in the treatment of osteosarcoma, a rare and aggressive form of bone cancer, have seen significant progress with chemotherapy, immunotherapy, and targeted therapy. Chemotherapy, the conventional approach, has witnessed refined drug regimens and novel agents tailored to enhance efficacy while minimizing adverse effects. This evolution aims to strike a balance between eradicating cancer cells and preserving patients' overall well-being. Immunotherapy has emerged as a promising avenue, leveraging the body's immune system to recognize and combat cancer cells. Innovative immunotherapeutic strategies, including immune checkpoint inhibitors, adoptive T cell therapy, and chimeric antigen receptor (CAR)-T cell therapy, exhibit the potential to enhance immune responses against osteosarcoma. Moreover, targeted therapy, designed to disrupt specific molecular pathways crucial for cancer growth, has gained traction in the treatment of osteosarcoma. Precision medicine approaches, such as identifying biomarkers and employing targeted agents, aim to tailor therapies to individual patients, maximizing effectiveness while minimizing collateral damage to healthy tissues. This article analyzes the current state of these three treatment modalities while comparing the efficacies of current chemotherapy, immunotherapy and targeted therapy agents.
{"title":"Chemotherapy, immunotherapy, and targeted therapy for osteosarcoma: Recent advancements","authors":"Esther Adewuyi , Harshal Chorya , Abdulbasit Muili , Abdulrahmon Moradeyo , Ayomide Kayode , Aastha Naik , Temitayo Odedele , Muntaqim Opabode","doi":"10.1016/j.critrevonc.2024.104575","DOIUrl":"10.1016/j.critrevonc.2024.104575","url":null,"abstract":"<div><div>Recent advancements in the treatment of osteosarcoma, a rare and aggressive form of bone cancer, have seen significant progress with chemotherapy, immunotherapy, and targeted therapy. Chemotherapy, the conventional approach, has witnessed refined drug regimens and novel agents tailored to enhance efficacy while minimizing adverse effects. This evolution aims to strike a balance between eradicating cancer cells and preserving patients' overall well-being. Immunotherapy has emerged as a promising avenue, leveraging the body's immune system to recognize and combat cancer cells. Innovative immunotherapeutic strategies, including immune checkpoint inhibitors, adoptive T cell therapy, and chimeric antigen receptor (CAR)-T cell therapy, exhibit the potential to enhance immune responses against osteosarcoma. Moreover, targeted therapy, designed to disrupt specific molecular pathways crucial for cancer growth, has gained traction in the treatment of osteosarcoma. Precision medicine approaches, such as identifying biomarkers and employing targeted agents, aim to tailor therapies to individual patients, maximizing effectiveness while minimizing collateral damage to healthy tissues. This article analyzes the current state of these three treatment modalities while comparing the efficacies of current chemotherapy, immunotherapy and targeted therapy agents.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104575"},"PeriodicalIF":5.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BRAF p.V600E exon 15 hotspot mutation can identify a molecular subgroup of metastatic colorectal cancer (mCRC) patients exhibiting poor prognosis under the conventional chemotherapy regimen. Recently, the chemotherapy-free combination of encorafenib and cetuximab has been approved as the standard of care for previously treated BRAF p.V600E mCRC patients, and genomic testing for BRAF mutations at the time of mCRC diagnosis is currently recommended. In clinical practice, BRAF mutation testing strategies are dramatically impacted by a lack of harmonization and standardization, both in the pre-analytical and analytical phases, which can result in BRAF-mutated patients not receiving the most appropriate therapy at recurrence. This paper proposes nine statements providing practical and concise advice on BRAF mutation testing in CRC, derived from collegial discussion and analysis of a multidisciplinary team of experts, including referral Italian oncologists and pathologists. The statements overview pivotal aspects implied in the detection, treatment and management of BRAF-mutated patients and have been drafted to represent a valuable tool for healthcare professionals committed to mCRC patient management. In addition, they represent a platform for implementing diagnostic-therapeutic workflows that can adapt to the variability of local resources while respecting the high-quality standards required by modern precision oncology.
{"title":"Detecting BRAF mutations in colorectal cancer in clinical practice: An Italian experts' position paper","authors":"Umberto Malapelle , Valentina Angerilli , Rossana Intini , Francesca Bergamo , Chiara Cremolini , Federica Grillo , Elena Guerini Rocco , Tiziana Pia Latiano , Erika Martinelli , Nicola Normanno , Fabio Pagni , Paola Parente , Alessandro Pastorino , Filippo Pietrantonio , Lisa Salvatore , Sara Lonardi , Matteo Fassan","doi":"10.1016/j.critrevonc.2024.104574","DOIUrl":"10.1016/j.critrevonc.2024.104574","url":null,"abstract":"<div><div><em>BRAF</em> p.V600E exon 15 hotspot mutation can identify a molecular subgroup of metastatic colorectal cancer (mCRC) patients exhibiting poor prognosis under the conventional chemotherapy regimen. Recently, the chemotherapy-free combination of encorafenib and cetuximab has been approved as the standard of care for previously treated <em>BRAF</em> p.V600E mCRC patients, and genomic testing for <em>BRAF</em> mutations at the time of mCRC diagnosis is currently recommended. In clinical practice, <em>BRAF</em> mutation testing strategies are dramatically impacted by a lack of harmonization and standardization, both in the pre-analytical and analytical phases, which can result in <em>BRAF</em>-mutated patients not receiving the most appropriate therapy at recurrence. This paper proposes nine statements providing practical and concise advice on <em>BRAF</em> mutation testing in CRC, derived from collegial discussion and analysis of a multidisciplinary team of experts, including referral Italian oncologists and pathologists. The statements overview pivotal aspects implied in the detection, treatment and management of <em>BRAF</em>-mutated patients and have been drafted to represent a valuable tool for healthcare professionals committed to mCRC patient management. In addition, they represent a platform for implementing diagnostic-therapeutic workflows that can adapt to the variability of local resources while respecting the high-quality standards required by modern precision oncology.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104574"},"PeriodicalIF":5.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1016/j.critrevonc.2024.104573
Paul Manoukian , Leo C. Kuhnen , Hanneke W.M. van Laarhoven , Maarten F. Bijlsma
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Due to a lack of clear symptoms, patients often present with advanced disease, with limited clinical intervention options. The high mortality rate of PDAC is, however, also a result of several other factors that include a high degree of heterogeneity and treatment resistant cellular phenotypes. Molecular subtypes of PDAC have been identified that are thought to represent cellular phenotypes at the tissue level. The epigenetic landscape is an important factor that dictates these subtypes. Permissive epigenetic landscapes serve as drivers of molecular heterogeneity and cellular plasticity in developing crypts as well as metaplastic lesions. Drawing parallels with other cancers, we hypothesize that epigenetic permissiveness is a potential driver of cellular plasticity in PDAC. In this review will explore the epigenetic alterations that underlie PDAC cell states and relate them to cellular plasticity from other contexts. In doing so, we aim to highlight epigenomic drivers of PDAC heterogeneity and plasticity and, with that, offer some insight to guide pre-clinical research.
{"title":"Association of epigenetic landscapes with heterogeneity and plasticity in pancreatic cancer","authors":"Paul Manoukian , Leo C. Kuhnen , Hanneke W.M. van Laarhoven , Maarten F. Bijlsma","doi":"10.1016/j.critrevonc.2024.104573","DOIUrl":"10.1016/j.critrevonc.2024.104573","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Due to a lack of clear symptoms, patients often present with advanced disease, with limited clinical intervention options. The high mortality rate of PDAC is, however, also a result of several other factors that include a high degree of heterogeneity and treatment resistant cellular phenotypes. Molecular subtypes of PDAC have been identified that are thought to represent cellular phenotypes at the tissue level. The epigenetic landscape is an important factor that dictates these subtypes. Permissive epigenetic landscapes serve as drivers of molecular heterogeneity and cellular plasticity in developing crypts as well as metaplastic lesions. Drawing parallels with other cancers, we hypothesize that epigenetic permissiveness is a potential driver of cellular plasticity in PDAC. In this review will explore the epigenetic alterations that underlie PDAC cell states and relate them to cellular plasticity from other contexts. In doing so, we aim to highlight epigenomic drivers of PDAC heterogeneity and plasticity and, with that, offer some insight to guide pre-clinical research.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"206 ","pages":"Article 104573"},"PeriodicalIF":5.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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