KRAS mutation: from undruggable to druggable in cancer

Abstract Cancer is the leading cause of death worldwide, and its treatment and outcomes have been dramatically revolutionised by targeted therapies. As the most frequently mutated oncogene, Kirsten rat sarcoma viral oncogene homologue (KRAS) has attracted substantial attention. The understanding of...

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Autores principales:	Lamei Huang, Zhixing Guo, Fang Wang, Liwu Fu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Medicine R Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/376e4538053644209dbda716fe11e25a
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spelling	oai:doaj.org-article:376e4538053644209dbda716fe11e25a2021-11-21T12:07:01ZKRAS mutation: from undruggable to druggable in cancer10.1038/s41392-021-00780-42059-3635https://doaj.org/article/376e4538053644209dbda716fe11e25a2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41392-021-00780-4https://doaj.org/toc/2059-3635Abstract Cancer is the leading cause of death worldwide, and its treatment and outcomes have been dramatically revolutionised by targeted therapies. As the most frequently mutated oncogene, Kirsten rat sarcoma viral oncogene homologue (KRAS) has attracted substantial attention. The understanding of KRAS is constantly being updated by numerous studies on KRAS in the initiation and progression of cancer diseases. However, KRAS has been deemed a challenging therapeutic target, even “undruggable”, after drug-targeting efforts over the past four decades. Recently, there have been surprising advances in directly targeted drugs for KRAS, especially in KRAS (G12C) inhibitors, such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have obtained encouraging results in clinical trials. Excitingly, AMG510 was the first drug-targeting KRAS (G12C) to be approved for clinical use this year. This review summarises the most recent understanding of fundamental aspects of KRAS, the relationship between the KRAS mutations and tumour immune evasion, and new progress in targeting KRAS, particularly KRAS (G12C). Moreover, the possible mechanisms of resistance to KRAS (G12C) inhibitors and possible combination therapies are summarised, with a view to providing the best regimen for individualised treatment with KRAS (G12C) inhibitors and achieving truly precise treatment.Lamei HuangZhixing GuoFang WangLiwu FuNature Publishing GrouparticleMedicineRBiology (General)QH301-705.5ENSignal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Biology (General) QH301-705.5
spellingShingle	Medicine R Biology (General) QH301-705.5 Lamei Huang Zhixing Guo Fang Wang Liwu Fu KRAS mutation: from undruggable to druggable in cancer
description	Abstract Cancer is the leading cause of death worldwide, and its treatment and outcomes have been dramatically revolutionised by targeted therapies. As the most frequently mutated oncogene, Kirsten rat sarcoma viral oncogene homologue (KRAS) has attracted substantial attention. The understanding of KRAS is constantly being updated by numerous studies on KRAS in the initiation and progression of cancer diseases. However, KRAS has been deemed a challenging therapeutic target, even “undruggable”, after drug-targeting efforts over the past four decades. Recently, there have been surprising advances in directly targeted drugs for KRAS, especially in KRAS (G12C) inhibitors, such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have obtained encouraging results in clinical trials. Excitingly, AMG510 was the first drug-targeting KRAS (G12C) to be approved for clinical use this year. This review summarises the most recent understanding of fundamental aspects of KRAS, the relationship between the KRAS mutations and tumour immune evasion, and new progress in targeting KRAS, particularly KRAS (G12C). Moreover, the possible mechanisms of resistance to KRAS (G12C) inhibitors and possible combination therapies are summarised, with a view to providing the best regimen for individualised treatment with KRAS (G12C) inhibitors and achieving truly precise treatment.
format	article
author	Lamei Huang Zhixing Guo Fang Wang Liwu Fu
author_facet	Lamei Huang Zhixing Guo Fang Wang Liwu Fu
author_sort	Lamei Huang
title	KRAS mutation: from undruggable to druggable in cancer
title_short	KRAS mutation: from undruggable to druggable in cancer
title_full	KRAS mutation: from undruggable to druggable in cancer
title_fullStr	KRAS mutation: from undruggable to druggable in cancer
title_full_unstemmed	KRAS mutation: from undruggable to druggable in cancer
title_sort	kras mutation: from undruggable to druggable in cancer
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/376e4538053644209dbda716fe11e25a
work_keys_str_mv	AT lameihuang krasmutationfromundruggabletodruggableincancer AT zhixingguo krasmutationfromundruggabletodruggableincancer AT fangwang krasmutationfromundruggabletodruggableincancer AT liwufu krasmutationfromundruggabletodruggableincancer
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KRAS mutation: from undruggable to druggable in cancer

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