医学
结直肠癌
肿瘤科
内科学
癌症
心肌病
肾上腺功能不全
免疫系统
免疫检查点
心力衰竭
免疫疗法
免疫学
作者
Arsenije Kojadinovic,Prabhjot S. Mundi
标识
DOI:10.1016/j.clcc.2021.07.002
摘要
Colorectal cancer is the third leading cause of cancer-related deaths in men and women in the United States. 1 Keum N Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019; 16: 713-732 Crossref PubMed Scopus (462) Google Scholar In the advanced and metastatic setting, the mainstay of treatment is combination regimens of chemotherapeutic agents. 2 Hurwitz HI Tan BR Reeves JA Xiong H Somer B Lenz HJ et al. Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019; 24: 921-932 Crossref PubMed Scopus (29) Google Scholar ,3 Loupakis F Cremolini C Masi G Lonardi S Zagonel V Salvatore L et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014; 371: 1609-1618 Crossref PubMed Scopus (654) Google Scholar The recognition of unique molecular subtypes, in particular the 3% to 5% of stage IV colon cancers with mismatch repair deficiency (dMMR) resulting in the expansion of microsatellites and high mutational burden, has recently paved the way to more effective and better tolerated treatments for select patients. 4 Germano G Amirouchene-Angelozzi N Rospo G Bardelli A. The Clinical Impact of the Genomic Landscape of Mismatch Repair-Deficient Cancers. Cancer Discov. 2018; 8: 1518-1528 Crossref PubMed Scopus (42) Google Scholar , 5 Hewish M Lord CJ Martin SA Cunningham D Ashworth A. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat Rev Clin Oncol. 2010; 7: 197-208 Crossref PubMed Scopus (158) Google Scholar , 6 Koopman M Kortman GA Mekenkamp L Ligtenberg MJ Hoogerbrugge N Antonini NF et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009; 100: 266-273 Crossref PubMed Scopus (286) Google Scholar , 7 Salem ME Puccini A Grothey A Raghavan D Goldberg RM Xiu J et al. Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers. Mol Cancer Res. 2018; 16: 805-812 Crossref PubMed Scopus (107) Google Scholar Immune checkpoint inhibitor (ICI) monotherapy and more recently dual therapy with ipilimumab and nivolumab are approved for patients with advanced dMMR colon cancer on the basis of high response rates, 31% to 43% with anti-PD1 monotherapy and 55% with dual checkpoint blockade, with median durations of response not reached at over 1 year of follow up. 8 Overman MJ McDermott R Leach JL Lonardi S Lenz HJ Morse MA et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017; 18: 1182-1191 Abstract Full Text Full Text PDF PubMed Scopus (1176) Google Scholar , 9 Overman MJ Lonardi S Wong KYM Lenz HJ Gelsomino F Aglietta M et al. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018; 36: 773-779 Crossref PubMed Scopus (814) Google Scholar , 10 Gourd E. Nivolumab plus ipilimumab in metastatic colorectal cancer. Lancet Oncol. 2018; 19: e139 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar , 11 Andre T Shiu KK Kim TW Jensen BV Jensen LH Punt C et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020; 383: 2207-2218 Crossref PubMed Scopus (324) Google Scholar
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