Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?

Abstract In recent years, the development of targeted therapies for tumors with KRAS mutations has progressed rapidly, rendering the notion of KRAS as “undruggable” outdated. However, targeted therapies for KRAS mutations still face numerous challenges, including resistance, efficacy concerns, toxic...

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Main Authors: Shenao Fu, Jiayao Ma, Changjing Cai, Jun Tan, Xiangying Deng, Hong Shen, Shan Zeng, Yihong Chen, Ying Han
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Experimental & Clinical Cancer Research
Subjects:
Online Access:https://doi.org/10.1186/s13046-025-03444-1
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author Shenao Fu
Jiayao Ma
Changjing Cai
Jun Tan
Xiangying Deng
Hong Shen
Shan Zeng
Yihong Chen
Ying Han
author_facet Shenao Fu
Jiayao Ma
Changjing Cai
Jun Tan
Xiangying Deng
Hong Shen
Shan Zeng
Yihong Chen
Ying Han
author_sort Shenao Fu
collection DOAJ
description Abstract In recent years, the development of targeted therapies for tumors with KRAS mutations has progressed rapidly, rendering the notion of KRAS as “undruggable” outdated. However, targeted therapies for KRAS mutations still face numerous challenges, including resistance, efficacy concerns, toxicity issues, and hurdles in drug development. Exploring alternative treatment modalities is thus essential. Extensive research has demonstrated that KRAS mutations significantly influence the immune microenvironment, presenting both challenges and opportunities for immunotherapy. Interestingly, it has been observed that different KRAS mutations and co-mutation subtypes exhibit significant variations in their immunological microenvironments, which undoubtedly impact immunotherapy choices. Here, we review the history of KRAS-targeted therapy, highlighting existing challenges, and summarize changes in the immune microenvironment of KRAS-mutated cancers and their potential therapeutic targets. We compare differences in the immune microenvironment across various mutation types and co-mutation subtypes, and offer perspectives on future research directions.
format Article
id doaj-art-0d8a049df2644fd38baa69db1b83f6d8
institution Kabale University
issn 1756-9966
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series Journal of Experimental & Clinical Cancer Research
spelling doaj-art-0d8a049df2644fd38baa69db1b83f6d82025-08-20T04:01:47ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-07-0144113110.1186/s13046-025-03444-1Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Shenao Fu0Jiayao Ma1Changjing Cai2Jun Tan3Xiangying Deng4Hong Shen5Shan Zeng6Yihong Chen7Ying Han8Department of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityDepartment of Oncology, Xiangya Hospital, Central South UniversityAbstract In recent years, the development of targeted therapies for tumors with KRAS mutations has progressed rapidly, rendering the notion of KRAS as “undruggable” outdated. However, targeted therapies for KRAS mutations still face numerous challenges, including resistance, efficacy concerns, toxicity issues, and hurdles in drug development. Exploring alternative treatment modalities is thus essential. Extensive research has demonstrated that KRAS mutations significantly influence the immune microenvironment, presenting both challenges and opportunities for immunotherapy. Interestingly, it has been observed that different KRAS mutations and co-mutation subtypes exhibit significant variations in their immunological microenvironments, which undoubtedly impact immunotherapy choices. Here, we review the history of KRAS-targeted therapy, highlighting existing challenges, and summarize changes in the immune microenvironment of KRAS-mutated cancers and their potential therapeutic targets. We compare differences in the immune microenvironment across various mutation types and co-mutation subtypes, and offer perspectives on future research directions.https://doi.org/10.1186/s13046-025-03444-1KRASCancerTargeted therapyImmunotherapyMicroenvironment
spellingShingle Shenao Fu
Jiayao Ma
Changjing Cai
Jun Tan
Xiangying Deng
Hong Shen
Shan Zeng
Yihong Chen
Ying Han
Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?
Journal of Experimental & Clinical Cancer Research
KRAS
Cancer
Targeted therapy
Immunotherapy
Microenvironment
title Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?
title_full Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?
title_fullStr Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?
title_full_unstemmed Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?
title_short Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?
title_sort precision immune regulation in kras mutated cancers the final piece of the puzzle
topic KRAS
Cancer
Targeted therapy
Immunotherapy
Microenvironment
url https://doi.org/10.1186/s13046-025-03444-1
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