Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS–MAPK�…

N Tanaka, JJ Lin, C Li, MB Ryan, J Zhang…�- Cancer discovery, 2021 - AACR
Mutant-selective KRASG12C inhibitors, such as MRTX849 (adagrasib) and AMG 510
(sotorasib), have demonstrated efficacy in KRAS G12C-mutant cancers, including non–small�…

More to the RAS Story: KRASG12C Inhibition, Resistance Mechanisms, and Moving Beyond KRASG12C

CD Lietman, ML Johnson, F McCormick…�- American Society of�…, 2022 - ascopubs.org
Despite the discovery of RAS oncogenes in human tumor DNA 40 years ago, the
development of effective targeted therapies directed against RAS has lagged behind those�…

[HTML][HTML] Resistance to KRASG12C Inhibitors in Non-Small Cell Lung Cancer

JB Blaquier, AF Cardona, G Recondo�- Frontiers in Oncology, 2021 - frontiersin.org
KRAS mutations are one of the most prevalent oncogenic alterations in cancer. Until
recently, drug development targeting KRAS did not convey clinical benefits to patients�…

Mechanisms of Resistance to KRASG12C-Targeted Therapy

NS Akhave, AB Biter, DS Hong�- Cancer discovery, 2021 - AACR
KRAS mutations are among the most common drivers of human carcinogenesis, and are
associated with poor prognosis and an aggressive disease course. With the advent of�…

[HTML][HTML] Overcoming resistance to drugs targeting KRASG12C mutation

D Jiao, S Yang�- The Innovation, 2020 - cell.com
Activating KRAS mutations are present in 25% of human cancer. Although oncogenic Ras
was deemed" undruggable" in the past, recent efforts led to the development of�…

Acquired Resistance to KRASG12C Inhibition in Cancer

MM Awad, S Liu, II Rybkin, KC Arbour…�- …�England Journal of�…, 2021 - Mass Medical Soc
Background Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown
promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at�…

The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients

J Hallin, LD Engstrom, L Hargis, A Calinisan, R Aranda…�- Cancer discovery, 2020 - AACR
Despite decades of research, efforts to directly target KRAS have been challenging.
MRTX849 was identified as a potent, selective, and covalent KRASG12C inhibitor that�…

[HTML][HTML] Rapid idiosyncratic mechanisms of clinical resistance to KRAS G12C inhibition

YS Tsai, MG Woodcock, SH Azam…�- The Journal of�…, 2022 - Am Soc Clin Investig
BACKGROUND The KRAS proto-oncogene is among the most frequently mutated genes in
cancer, yet for 40 years it remained an elusive therapeutic target. Recently, allosteric�…

Overcoming KRAS-Mutant Lung Cancer

J Luo, J Ostrem, B Pellini, D Imbody, Y Stern…�- American Society of�…, 2022 - ascopubs.org
More than 50 years after the discovery of RAS family proteins, which harbor the most
common activating mutations in cancer, the US Food and Drug Administration approved the�…

Resistance looms for KRAS G12C inhibitors and rational tackling strategies

J Zhang, J Zhang, Q Liu, XX Fan, ELH Leung…�- Pharmacology &�…, 2022 - Elsevier
KRAS mutations are one of the most frequent activating alterations in carcinoma. Recent
efforts have witnessed a revolutionary strategy for KRAS G12C inhibitors with exhibiting�…