David Johnson , Cheng Ean Chee , Wesley Wong , Rachel C.T. Lam , Iain Bee Huat Tan , Brigette B.Y. Ma
{"title":"转移性结直肠癌靶向治疗的最新进展--临床转化与未来方向","authors":"David Johnson , Cheng Ean Chee , Wesley Wong , Rachel C.T. Lam , Iain Bee Huat Tan , Brigette B.Y. Ma","doi":"10.1016/j.ctrv.2024.102700","DOIUrl":null,"url":null,"abstract":"<div><p>The last two decades have witnessed major breakthroughs in the development of targeted therapy for patients with metastatic colorectal cancer (mCRC), an achievement which stems largely from advances in translational research. Precision medicine is now widely practiced in routine oncological care, where systemic therapy is individualized based on clinical factors such as primary tumor sidedness, location and number of metastases, as well as molecular factors such as the RAS and BRAF mutation status, mismatch repair / microsatellite status and presence of other actionable genomic alterations in the tumor. The optimal selection of patients with RAS and BRAF-wild type (WT), left-sided primary tumor for treatment with epidermal growth factor receptor (EGFR) and chemotherapy (chemo) has markedly improved survival in the first-line setting. The pivotal trials of cetuximab in combination with BRAF/ MEK inhibitor for BRAF V600E mutant mCRC, and panitumumab with KRAS G12C inhibitor in KRAS(G12C)-mutant mCRC have been practice-changing. Anti-HER2 small molecular inhibitor, antibodies and antibody-drug conjugates have significantly improved the treatment outcome of patients with HER2 amplified mCRC. Anti-angiogenesis agents are now used across all lines of treatment and novel combinations with immune-checkpoint inhibitors are under active investigation in MSS mCRC. The non-invasive monitoring of molecular resistance to targeted therapies using Next Generation Sequencing analysis of circulating tumor-derived DNA (ctDNA) and captured sequencing of tumors have improved patient selection for targeted therapies. This review will focus on how latest advances, challenges and future directions in the development of targeted therapies in mCRC.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":9.6000,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Current advances in targeted therapy for metastatic colorectal cancer – Clinical translation and future directions\",\"authors\":\"David Johnson , Cheng Ean Chee , Wesley Wong , Rachel C.T. Lam , Iain Bee Huat Tan , Brigette B.Y. Ma\",\"doi\":\"10.1016/j.ctrv.2024.102700\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The last two decades have witnessed major breakthroughs in the development of targeted therapy for patients with metastatic colorectal cancer (mCRC), an achievement which stems largely from advances in translational research. Precision medicine is now widely practiced in routine oncological care, where systemic therapy is individualized based on clinical factors such as primary tumor sidedness, location and number of metastases, as well as molecular factors such as the RAS and BRAF mutation status, mismatch repair / microsatellite status and presence of other actionable genomic alterations in the tumor. The optimal selection of patients with RAS and BRAF-wild type (WT), left-sided primary tumor for treatment with epidermal growth factor receptor (EGFR) and chemotherapy (chemo) has markedly improved survival in the first-line setting. The pivotal trials of cetuximab in combination with BRAF/ MEK inhibitor for BRAF V600E mutant mCRC, and panitumumab with KRAS G12C inhibitor in KRAS(G12C)-mutant mCRC have been practice-changing. Anti-HER2 small molecular inhibitor, antibodies and antibody-drug conjugates have significantly improved the treatment outcome of patients with HER2 amplified mCRC. Anti-angiogenesis agents are now used across all lines of treatment and novel combinations with immune-checkpoint inhibitors are under active investigation in MSS mCRC. The non-invasive monitoring of molecular resistance to targeted therapies using Next Generation Sequencing analysis of circulating tumor-derived DNA (ctDNA) and captured sequencing of tumors have improved patient selection for targeted therapies. This review will focus on how latest advances, challenges and future directions in the development of targeted therapies in mCRC.</p></div>\",\"PeriodicalId\":9537,\"journal\":{\"name\":\"Cancer treatment reviews\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.6000,\"publicationDate\":\"2024-02-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer treatment reviews\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0305737224000185\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer treatment reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0305737224000185","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Current advances in targeted therapy for metastatic colorectal cancer – Clinical translation and future directions
The last two decades have witnessed major breakthroughs in the development of targeted therapy for patients with metastatic colorectal cancer (mCRC), an achievement which stems largely from advances in translational research. Precision medicine is now widely practiced in routine oncological care, where systemic therapy is individualized based on clinical factors such as primary tumor sidedness, location and number of metastases, as well as molecular factors such as the RAS and BRAF mutation status, mismatch repair / microsatellite status and presence of other actionable genomic alterations in the tumor. The optimal selection of patients with RAS and BRAF-wild type (WT), left-sided primary tumor for treatment with epidermal growth factor receptor (EGFR) and chemotherapy (chemo) has markedly improved survival in the first-line setting. The pivotal trials of cetuximab in combination with BRAF/ MEK inhibitor for BRAF V600E mutant mCRC, and panitumumab with KRAS G12C inhibitor in KRAS(G12C)-mutant mCRC have been practice-changing. Anti-HER2 small molecular inhibitor, antibodies and antibody-drug conjugates have significantly improved the treatment outcome of patients with HER2 amplified mCRC. Anti-angiogenesis agents are now used across all lines of treatment and novel combinations with immune-checkpoint inhibitors are under active investigation in MSS mCRC. The non-invasive monitoring of molecular resistance to targeted therapies using Next Generation Sequencing analysis of circulating tumor-derived DNA (ctDNA) and captured sequencing of tumors have improved patient selection for targeted therapies. This review will focus on how latest advances, challenges and future directions in the development of targeted therapies in mCRC.
期刊介绍:
Cancer Treatment Reviews
Journal Overview:
International journal focused on developments in cancer treatment research
Publishes state-of-the-art, authoritative reviews to keep clinicians and researchers informed
Regular Sections in Each Issue:
Comments on Controversy
Tumor Reviews
Anti-tumor Treatments
New Drugs
Complications of Treatment
General and Supportive Care
Laboratory/Clinic Interface
Submission and Editorial System:
Online submission and editorial system for Cancer Treatment Reviews