Targeting KRAS(G12C): From Inhibitory Mechanism to Modulation of Antitumor Effects in Patients.
Cell
; 183(4): 850-859, 2020 11 12.
Article
in En
| MEDLINE
| ID: mdl-33065029
KRAS mutations are among the most common genetic alterations in lung, colorectal, and pancreatic cancers. Direct inhibition of KRAS oncoproteins has been a long-standing pursuit in precision oncology, one established shortly after the discovery of RAS mutations in human cancer cells nearly 40 years ago. Recent advances in medicinal chemistry have established inhibitors targeting KRAS(G12C), a mutation found in â¼13% of lung adenocarcinomas and, at a lower frequency, in other cancers. Preclinical studies describing their discovery and mechanism of action, coupled with emerging clinical data from patients treated with these drugs, have sparked a renewed enthusiasm in the study of KRAS and its therapeutic potential. Here, we discuss how these advances are reshaping the fundamental aspects of KRAS oncoprotein biology and the strides being made toward improving patient outcomes in the clinic.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins p21(ras)
/
Molecular Targeted Therapy
/
Mutation
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Cell
Year:
2020
Type:
Article
Affiliation country:
United States