{"title":"Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors.","authors":"Dongsheng He, Rilan Bai, Naifei Chen, Jiuwei Cui","doi":"10.21147/j.issn.1000-9604.2024.04.06","DOIUrl":null,"url":null,"abstract":"<p><p>Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) is the most frequently mutated oncogene, occurring in various tumor types. Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations, resistance to these inhibitors has eventually emerged. A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome resistance. Immunotherapy has developed rapidly in recent years, and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations, finding that immune factors play an essential role in KRAS-mutant (KRAS-Mut) tumor therapy and targeted drug resistance. Breakthroughs and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory patients. Here, we reviewed KRAS mutation-targeted treatment strategies and resistance issues, focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS inhibition. We aimed to guide innovative approaches combining RAS inhibition with immunotherapy, review advances in preclinical and clinical stages, and discuss challenges and future directions.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":"36 4","pages":"421-441"},"PeriodicalIF":7.0000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377883/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21147/j.issn.1000-9604.2024.04.06","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated oncogene, occurring in various tumor types. Despite extensive efforts over the past 40 years to develop inhibitors targeting KRAS mutations, resistance to these inhibitors has eventually emerged. A more precise understanding of KRAS mutations and the mechanism of resistance development is essential for creating novel inhibitors that target specifically KRAS mutations and can delay or overcome resistance. Immunotherapy has developed rapidly in recent years, and in-depth dissection of the tumor immune microenvironment has led researchers to shift their focus to patients with KRAS mutations, finding that immune factors play an essential role in KRAS-mutant (KRAS-Mut) tumor therapy and targeted drug resistance. Breakthroughs and transitions from targeted therapy to immunotherapy have provided new hope for treating refractory patients. Here, we reviewed KRAS mutation-targeted treatment strategies and resistance issues, focusing on our in-depth exploration of the specific immune status of patients with KRAS mutations and the impact of body immunity following KRAS inhibition. We aimed to guide innovative approaches combining RAS inhibition with immunotherapy, review advances in preclinical and clinical stages, and discuss challenges and future directions.
期刊介绍:
Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013.
CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.