Targeting KRAS mutant cancers: from druggable therapy to drug resistance.
Mol Cancer
; 21(1): 159, 2022 08 04.
Article
em En
| MEDLINE
| ID: mdl-35922812
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas p21(ras)
/
Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article