KRAS-mutant non-small cell lung cancer: Converging small molecules and immune checkpoint inhibition.
EBioMedicine
; 41: 711-716, 2019 Mar.
Article
em En
| MEDLINE
| ID: mdl-30852159
ABSTRACT
KRAS is the most frequent oncogene in non-small cell lung cancer (NSCLC), a molecular subset characterized by historical disappointments in targeted treatment approaches such as farnesyl transferase inhibition, downstream MEK inhibition, and synthetic lethality screens. Unlike other important mutational subtypes of NSCLC, preclinical work supports the hypothesis that KRAS mutations may be vulnerable to immunotherapy approaches, an efficacy associated in particular with TP53 co-mutation. In this review we detail reasons for previous failures in KRAS-mutant NSCLC, evidence to suggest that KRAS mutation is a genetic marker of benefit from immune checkpoint inhibition, and emerging direct inhibitors of K-Ras which will soon be combined with immunotherapy during clinical development. With signs of real progress in this subgroup of unmet need, we anticipate that KRAS mutant NSCLC will be the most important molecular subset of cancer to evaluate the combination of small molecules and immune checkpoint inhibitors (CPI).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas p21(ras)
/
Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido