Pub Date : 2024-06-14DOI: 10.1038/s41575-024-00953-w
Jordan Hindson
{"title":"Intermittent fasting for NASH and HCC in mice","authors":"Jordan Hindson","doi":"10.1038/s41575-024-00953-w","DOIUrl":"10.1038/s41575-024-00953-w","url":null,"abstract":"","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 7","pages":"461-461"},"PeriodicalIF":45.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14DOI: 10.1038/s41575-024-00951-y
Saurav D. Haldar, Nilofer S. Azad
The advent of next-generation RAS inhibitors brings renewed optimism to the care of patients with pancreatic cancer after decades of failure for novel therapeutics. A recent study highlights the potent antitumour activity of the multi-selective RAS(ON) inhibitor RMC-7977 across a spectrum of preclinical pancreatic cancer models.
{"title":"Unlocking the promise of RAS inhibition in pancreatic cancer","authors":"Saurav D. Haldar, Nilofer S. Azad","doi":"10.1038/s41575-024-00951-y","DOIUrl":"10.1038/s41575-024-00951-y","url":null,"abstract":"The advent of next-generation RAS inhibitors brings renewed optimism to the care of patients with pancreatic cancer after decades of failure for novel therapeutics. A recent study highlights the potent antitumour activity of the multi-selective RAS(ON) inhibitor RMC-7977 across a spectrum of preclinical pancreatic cancer models.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 8","pages":"535-536"},"PeriodicalIF":45.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-07DOI: 10.1038/s41575-024-00948-7
Juliana Serrazina, Helena Cortez-Pinto
An expert panel has proposed 28 recommendations for the design and conduct of clinical trials for alcohol use disorders and alcohol-associated liver disease. This field has a scarcity of clinical trials, despite alcohol abuse and alcohol-related liver disease being one of the greatest causes of morbidity and mortality worldwide.
{"title":"Shaping new paths in clinical trial design to address alcohol use disorders and alcohol-associated liver disease","authors":"Juliana Serrazina, Helena Cortez-Pinto","doi":"10.1038/s41575-024-00948-7","DOIUrl":"10.1038/s41575-024-00948-7","url":null,"abstract":"An expert panel has proposed 28 recommendations for the design and conduct of clinical trials for alcohol use disorders and alcohol-associated liver disease. This field has a scarcity of clinical trials, despite alcohol abuse and alcohol-related liver disease being one of the greatest causes of morbidity and mortality worldwide.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 9","pages":"607-608"},"PeriodicalIF":45.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-07DOI: 10.1038/s41575-024-00936-x
Brian P. Lee, Katie Witkiewitz, Jessica Mellinger, Frank A. Anania, Ramon Bataller, Thomas G. Cotter, Brenda Curtis, Srinivasan Dasarathy, Kelly S. DeMartini, Ivan Diamond, Nancy Diazgranados, Andrea F. DiMartini, Daniel E. Falk, Anne C. Fernandez, Margarita N. German, Patrick S. Kamath, Kelley M. Kidwell, Lorenzo Leggio, Raye Litten, Alexandre Louvet, Michael R. Lucey, Mary E. McCaul, Arun J. Sanyal, Ashwani K. Singal, Norman L. Sussman, Norah A. Terrault, Mark R. Thursz, Elizabeth C. Verna, Svetlana Radaeva, Laura E. Nagy, Mack C. Mitchell
Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions. Alcohol-associated liver disease is the main cause of liver-related morbidity and mortality globally. This Consensus Statement makes recommendations for the design, best practice and conduct of clinical trials to evaluate the effects of alcohol use in alcohol-associated liver disease and alcohol use disorder.
{"title":"Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement","authors":"Brian P. Lee, Katie Witkiewitz, Jessica Mellinger, Frank A. Anania, Ramon Bataller, Thomas G. Cotter, Brenda Curtis, Srinivasan Dasarathy, Kelly S. DeMartini, Ivan Diamond, Nancy Diazgranados, Andrea F. DiMartini, Daniel E. Falk, Anne C. Fernandez, Margarita N. German, Patrick S. Kamath, Kelley M. Kidwell, Lorenzo Leggio, Raye Litten, Alexandre Louvet, Michael R. Lucey, Mary E. McCaul, Arun J. Sanyal, Ashwani K. Singal, Norman L. Sussman, Norah A. Terrault, Mark R. Thursz, Elizabeth C. Verna, Svetlana Radaeva, Laura E. Nagy, Mack C. Mitchell","doi":"10.1038/s41575-024-00936-x","DOIUrl":"10.1038/s41575-024-00936-x","url":null,"abstract":"Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions. Alcohol-associated liver disease is the main cause of liver-related morbidity and mortality globally. This Consensus Statement makes recommendations for the design, best practice and conduct of clinical trials to evaluate the effects of alcohol use in alcohol-associated liver disease and alcohol use disorder.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 9","pages":"626-645"},"PeriodicalIF":45.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00936-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-04DOI: 10.1038/s41575-024-00938-9
Alina M. Allen, Zobair M. Younossi, Anna Mae Diehl, Michael R. Charlton, Jeffrey V. Lazarus
Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has led to, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030. This Perspective discusses the nomenclature change from nonalcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease (MASLD) and proposes steps necessary to improve care and end the public health threat posed by MASLD and metabolic dysfunction-associated steatohepatitis.
{"title":"Envisioning how to advance the MASH field","authors":"Alina M. Allen, Zobair M. Younossi, Anna Mae Diehl, Michael R. Charlton, Jeffrey V. Lazarus","doi":"10.1038/s41575-024-00938-9","DOIUrl":"10.1038/s41575-024-00938-9","url":null,"abstract":"Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has led to, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030. This Perspective discusses the nomenclature change from nonalcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease (MASLD) and proposes steps necessary to improve care and end the public health threat posed by MASLD and metabolic dysfunction-associated steatohepatitis.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 10","pages":"726-738"},"PeriodicalIF":45.9,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-03DOI: 10.1038/s41575-024-00937-w
Abraham S. Meijnikman, Max Nieuwdorp, Bernd Schnabl
The gut microbiome exerts metabolic actions on distal tissues and organs outside the intestine, partly through microbial metabolites that diffuse into the circulation. The disruption of gut homeostasis results in changes to microbial metabolites, and more than half of the variance in the plasma metabolome can be explained by the gut microbiome. Ethanol is a major microbial metabolite that is produced in the intestine of nearly all individuals; however, elevated ethanol production is associated with pathological conditions such as metabolic dysfunction-associated steatotic liver disease and auto-brewery syndrome, in which the liver’s capacity to metabolize ethanol is surpassed. In this Review, we describe the mechanisms underlying excessive ethanol production in the gut and the role of ethanol catabolism in mediating pathogenic effects of ethanol on the liver and host metabolism. We conclude by discussing approaches to target excessive ethanol production by gut bacteria. Ethanol is produced in the gut by several different species of fermentative bacteria. This Review discusses the sources and consequences of endogenously produced ethanol, explores its relationship with liver diseases such as metabolic dysfunction-associated steatotic liver disease and covers approaches to target excessive ethanol production in the gut.
{"title":"Endogenous ethanol production in health and disease","authors":"Abraham S. Meijnikman, Max Nieuwdorp, Bernd Schnabl","doi":"10.1038/s41575-024-00937-w","DOIUrl":"10.1038/s41575-024-00937-w","url":null,"abstract":"The gut microbiome exerts metabolic actions on distal tissues and organs outside the intestine, partly through microbial metabolites that diffuse into the circulation. The disruption of gut homeostasis results in changes to microbial metabolites, and more than half of the variance in the plasma metabolome can be explained by the gut microbiome. Ethanol is a major microbial metabolite that is produced in the intestine of nearly all individuals; however, elevated ethanol production is associated with pathological conditions such as metabolic dysfunction-associated steatotic liver disease and auto-brewery syndrome, in which the liver’s capacity to metabolize ethanol is surpassed. In this Review, we describe the mechanisms underlying excessive ethanol production in the gut and the role of ethanol catabolism in mediating pathogenic effects of ethanol on the liver and host metabolism. We conclude by discussing approaches to target excessive ethanol production by gut bacteria. Ethanol is produced in the gut by several different species of fermentative bacteria. This Review discusses the sources and consequences of endogenously produced ethanol, explores its relationship with liver diseases such as metabolic dysfunction-associated steatotic liver disease and covers approaches to target excessive ethanol production in the gut.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 8","pages":"556-571"},"PeriodicalIF":45.9,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-03DOI: 10.1038/s41575-024-00935-y
Dominik Bettenworth, Mark E. Baker, Joel G. Fletcher, Vipul Jairath, Cathy Lu, Willem Bemelman, Geert d’Haens, Andre d’Hoore, Axel Dignass, Iris Dotan, Roger Feakins, Phillip Fleshner, Christina Ha, Gaylyn Henderson, Ruishen Lyu, Julian Panes, Gerhard Rogler, Ren Mao, Jordi Rimola, William J. Sandborn, Siew C. Ng, Britta Siegmund, Mark Silverberg, Stuart A. Taylor, Bram Verstockt, Ilyssa O. Gordon, David H. Bruining, Brian G. Feagan, Florian Rieder, Stenosis Therapy Anti-Fibrotic Research (STAR) Consortium
Fibrostenosis of the small bowel is common in patients with Crohn’s disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn’s disease. It was conducted by a panel of 28 global experts and one patient representative. Following a systematic literature review, 526 candidate items grouped into 136 questions were generated and subsequently evaluated for appropriateness. Strictures are best defined as wall thickening, luminal narrowing and prestenotic dilation. Cross-sectional imaging is required for accurate diagnosis of fibrostenosing Crohn’s disease, and it is recommended before making treatment decisions. It should also assess the degree of inflammation in the bowel wall. Multiple options for medical anti-inflammatory, endoscopic and surgical therapies were suggested, including follow-up strategies following therapy. This Consensus Statement supports clinical practice through providing guidance on definitions, diagnosis and therapeutic management of patients with fibrostenosing small bowel Crohn’s disease. In this Consensus Statement, a global multidisciplinary panel of experts provides recommendations for the definitions, diagnosis and management of patients with fibrostenosing small bowel Crohn’s disease.
{"title":"A global consensus on the definitions, diagnosis and management of fibrostenosing small bowel Crohn’s disease in clinical practice","authors":"Dominik Bettenworth, Mark E. Baker, Joel G. Fletcher, Vipul Jairath, Cathy Lu, Willem Bemelman, Geert d’Haens, Andre d’Hoore, Axel Dignass, Iris Dotan, Roger Feakins, Phillip Fleshner, Christina Ha, Gaylyn Henderson, Ruishen Lyu, Julian Panes, Gerhard Rogler, Ren Mao, Jordi Rimola, William J. Sandborn, Siew C. Ng, Britta Siegmund, Mark Silverberg, Stuart A. Taylor, Bram Verstockt, Ilyssa O. Gordon, David H. Bruining, Brian G. Feagan, Florian Rieder, Stenosis Therapy Anti-Fibrotic Research (STAR) Consortium","doi":"10.1038/s41575-024-00935-y","DOIUrl":"10.1038/s41575-024-00935-y","url":null,"abstract":"Fibrostenosis of the small bowel is common in patients with Crohn’s disease. No consensus recommendations on definition, diagnosis and management in clinical practice are currently available. In this Consensus Statement, we present a clinical practice RAND/UCLA appropriateness study on the definition, diagnosis and clinical management of fibrostenosing Crohn’s disease. It was conducted by a panel of 28 global experts and one patient representative. Following a systematic literature review, 526 candidate items grouped into 136 questions were generated and subsequently evaluated for appropriateness. Strictures are best defined as wall thickening, luminal narrowing and prestenotic dilation. Cross-sectional imaging is required for accurate diagnosis of fibrostenosing Crohn’s disease, and it is recommended before making treatment decisions. It should also assess the degree of inflammation in the bowel wall. Multiple options for medical anti-inflammatory, endoscopic and surgical therapies were suggested, including follow-up strategies following therapy. This Consensus Statement supports clinical practice through providing guidance on definitions, diagnosis and therapeutic management of patients with fibrostenosing small bowel Crohn’s disease. In this Consensus Statement, a global multidisciplinary panel of experts provides recommendations for the definitions, diagnosis and management of patients with fibrostenosing small bowel Crohn’s disease.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 8","pages":"572-584"},"PeriodicalIF":45.9,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00935-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141235932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1038/s41575-024-00939-8
For Pride Month, we celebrate the LGBTQ+ community and take stock of the challenges they continue to experience. Gastroenterologists and hepatologists can and should advocate, improve inclusion and be effective allies for our LGBTQ+ colleagues and patients.
{"title":"Pride in gastroenterology and hepatology","authors":"","doi":"10.1038/s41575-024-00939-8","DOIUrl":"10.1038/s41575-024-00939-8","url":null,"abstract":"For Pride Month, we celebrate the LGBTQ+ community and take stock of the challenges they continue to experience. Gastroenterologists and hepatologists can and should advocate, improve inclusion and be effective allies for our LGBTQ+ colleagues and patients.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 6","pages":"367-367"},"PeriodicalIF":65.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41575-024-00939-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141182324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-28DOI: 10.1038/s41575-024-00934-z
Adrià Cañellas-Socias, Elena Sancho, Eduard Batlle
Despite extensive research and improvements in understanding colorectal cancer (CRC), its metastatic form continues to pose a substantial challenge, primarily owing to limited therapeutic options and a poor prognosis. This Review addresses the emerging focus on metastatic CRC (mCRC), which has historically been under-studied compared with primary CRC despite its lethality. We delve into two crucial aspects: the molecular and cellular determinants facilitating CRC metastasis and the principles guiding the evolution of metastatic disease. Initially, we examine the genetic alterations integral to CRC metastasis, connecting them to clinically marked characteristics of advanced CRC. Subsequently, we scrutinize the role of cellular heterogeneity and plasticity in metastatic spread and therapy resistance. Finally, we explore how the tumour microenvironment influences metastatic disease, emphasizing the effect of stromal gene programmes and the immune context. The ongoing research in these fields holds immense importance, as its future implications are projected to revolutionize the treatment of patients with mCRC, hopefully offering a promising outlook for their survival. Metastatic colorectal cancer (mCRC) has a poor prognosis, and therapeutic options are limited. This Review provides a comprehensive overview of the genetic and molecular underpinnings of mCRC, discussing the therapeutic potential arising from this knowledge.
{"title":"Mechanisms of metastatic colorectal cancer","authors":"Adrià Cañellas-Socias, Elena Sancho, Eduard Batlle","doi":"10.1038/s41575-024-00934-z","DOIUrl":"10.1038/s41575-024-00934-z","url":null,"abstract":"Despite extensive research and improvements in understanding colorectal cancer (CRC), its metastatic form continues to pose a substantial challenge, primarily owing to limited therapeutic options and a poor prognosis. This Review addresses the emerging focus on metastatic CRC (mCRC), which has historically been under-studied compared with primary CRC despite its lethality. We delve into two crucial aspects: the molecular and cellular determinants facilitating CRC metastasis and the principles guiding the evolution of metastatic disease. Initially, we examine the genetic alterations integral to CRC metastasis, connecting them to clinically marked characteristics of advanced CRC. Subsequently, we scrutinize the role of cellular heterogeneity and plasticity in metastatic spread and therapy resistance. Finally, we explore how the tumour microenvironment influences metastatic disease, emphasizing the effect of stromal gene programmes and the immune context. The ongoing research in these fields holds immense importance, as its future implications are projected to revolutionize the treatment of patients with mCRC, hopefully offering a promising outlook for their survival. Metastatic colorectal cancer (mCRC) has a poor prognosis, and therapeutic options are limited. This Review provides a comprehensive overview of the genetic and molecular underpinnings of mCRC, discussing the therapeutic potential arising from this knowledge.","PeriodicalId":18793,"journal":{"name":"Nature Reviews Gastroenterology &Hepatology","volume":"21 9","pages":"609-625"},"PeriodicalIF":45.9,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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