Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors.

IF 7 2区 医学 Q1 ONCOLOGY Chinese Journal of Cancer Research Pub Date : 2024-08-30 DOI:10.21147/j.issn.1000-9604.2024.04.06
Dongsheng He, Rilan Bai, Naifei Chen, Jiuwei Cui
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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.

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克氏鼠肉瘤病毒癌基因同源体(KRAS)突变肿瘤的免疫状态和联合免疫疗法的进展。
克氏大鼠肉瘤病毒癌基因同源物(KRAS)是最常发生突变的癌基因,在各种肿瘤类型中都会出现。尽管过去 40 年来人们一直在努力开发针对 KRAS 突变的抑制剂,但最终还是出现了对这些抑制剂的耐药性。要想开发出专门针对 KRAS 突变并能延缓或克服耐药性的新型抑制剂,就必须更准确地了解 KRAS 突变和耐药性产生的机制。近年来,免疫疗法发展迅速,对肿瘤免疫微环境的深入剖析使研究人员将重点转移到KRAS突变患者身上,发现免疫因素在KRAS突变(KRAS-Mut)肿瘤治疗和靶向药物耐药中起着至关重要的作用。从靶向治疗到免疫治疗的突破和转变为治疗难治性患者带来了新的希望。在此,我们回顾了 KRAS 突变靶向治疗策略和耐药性问题,重点深入探讨了 KRAS 突变患者的特殊免疫状态以及 KRAS 抑制后机体免疫的影响。我们旨在指导将 RAS 抑制与免疫疗法相结合的创新方法,回顾临床前和临床阶段的进展,并讨论挑战和未来方向。
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来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
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.
期刊最新文献
Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation: A multicenter, case-series study in China. Immune status and combined immunotherapy progression in Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant tumors. Potential value of detection of minimal residual disease in colorectal cancer following radical resection. Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+ T cell function in esophageal squamous cell carcinoma. SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.
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