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Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with drugs is challenging because KRAS is considered undruggable due to the lack of classic drug binding sites. Over the past 40 years, great eff...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351107/ https://www.ncbi.nlm.nih.gov/pubmed/35922812 http://dx.doi.org/10.1186/s12943-022-01629-2 |
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author | Zhu, Chunxiao Guan, Xiaoqing Zhang, Xinuo Luan, Xin Song, Zhengbo Cheng, Xiangdong Zhang, Weidong Qin, Jiang-Jiang |
author_facet | Zhu, Chunxiao Guan, Xiaoqing Zhang, Xinuo Luan, Xin Song, Zhengbo Cheng, Xiangdong Zhang, Weidong Qin, Jiang-Jiang |
author_sort | Zhu, Chunxiao |
collection | PubMed |
description | Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with drugs is challenging because KRAS is considered undruggable due to the lack of classic drug binding sites. Over the past 40 years, great efforts have been made to explore routes for indirect targeting of KRAS mutant cancers, including KRAS expression, processing, upstream regulators, or downstream effectors. With the advent of KRAS (G12C) inhibitors, KRAS mutations are now druggable. Despite such inhibitors showing remarkable clinical responses, resistance to monotherapy of KRAS inhibitors is eventually developed. Significant progress has been made in understanding the mechanisms of drug resistance to KRAS-mutant inhibitors. Here we review the most recent advances in therapeutic approaches and resistance mechanisms targeting KRAS mutations and discuss opportunities for combination therapy. |
format | Online Article Text |
id | pubmed-9351107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93511072022-08-05 Targeting KRAS mutant cancers: from druggable therapy to drug resistance Zhu, Chunxiao Guan, Xiaoqing Zhang, Xinuo Luan, Xin Song, Zhengbo Cheng, Xiangdong Zhang, Weidong Qin, Jiang-Jiang Mol Cancer Review Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with drugs is challenging because KRAS is considered undruggable due to the lack of classic drug binding sites. Over the past 40 years, great efforts have been made to explore routes for indirect targeting of KRAS mutant cancers, including KRAS expression, processing, upstream regulators, or downstream effectors. With the advent of KRAS (G12C) inhibitors, KRAS mutations are now druggable. Despite such inhibitors showing remarkable clinical responses, resistance to monotherapy of KRAS inhibitors is eventually developed. Significant progress has been made in understanding the mechanisms of drug resistance to KRAS-mutant inhibitors. Here we review the most recent advances in therapeutic approaches and resistance mechanisms targeting KRAS mutations and discuss opportunities for combination therapy. BioMed Central 2022-08-04 /pmc/articles/PMC9351107/ /pubmed/35922812 http://dx.doi.org/10.1186/s12943-022-01629-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Zhu, Chunxiao Guan, Xiaoqing Zhang, Xinuo Luan, Xin Song, Zhengbo Cheng, Xiangdong Zhang, Weidong Qin, Jiang-Jiang Targeting KRAS mutant cancers: from druggable therapy to drug resistance |
title | Targeting KRAS mutant cancers: from druggable therapy to drug resistance |
title_full | Targeting KRAS mutant cancers: from druggable therapy to drug resistance |
title_fullStr | Targeting KRAS mutant cancers: from druggable therapy to drug resistance |
title_full_unstemmed | Targeting KRAS mutant cancers: from druggable therapy to drug resistance |
title_short | Targeting KRAS mutant cancers: from druggable therapy to drug resistance |
title_sort | targeting kras mutant cancers: from druggable therapy to drug resistance |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351107/ https://www.ncbi.nlm.nih.gov/pubmed/35922812 http://dx.doi.org/10.1186/s12943-022-01629-2 |
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