Overcoming adaptive resistance to KRAS inhibitors through vertical pathway targeting
Abstract KRAS G12C inhibitors have shown promise in KRAS G12C–mutant lung cancer but
intrinsic and acquired resistance are common. Cotreatment with inhibitors of the protein …
intrinsic and acquired resistance are common. Cotreatment with inhibitors of the protein …
KRAS G12C NSCLC models are sensitive to direct targeting of KRAS in combination with PI3K inhibition
Purpose: KRAS-mutant lung cancers have been recalcitrant to treatments including those
targeting the MAPK pathway. Covalent inhibitors of KRAS p. G12C allele allow for direct and …
targeting the MAPK pathway. Covalent inhibitors of KRAS p. G12C allele allow for direct and …
[HTML][HTML] A Breakthrough Brought about by Targeting KRASG12C: Nonconformity Is Punished
W Ning, Z Yang, GJ Kocher, P Dorn, RW Peng - Cancers, 2022 - mdpi.com
Simple Summary KRAS is the most common oncogene in human cancers and has long
been considered ''undruggable''—that is, until recently, when covalent inhibitors that …
been considered ''undruggable''—that is, until recently, when covalent inhibitors that …
Overcoming KRAS-Mutant Lung Cancer
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 …
common activating mutations in cancer, the US Food and Drug Administration approved the …
Cell Type–specific Adaptive Signaling Responses to KRASG12C Inhibition
HS Solanki, EA Welsh, B Fang, V Izumi, L Darville… - Clinical Cancer …, 2021 - AACR
Purpose: Covalent inhibitors of KRASG12C specifically target tumors driven by this form of
mutant KRAS, yet early studies show that bypass signaling drives adaptive resistance …
mutant KRAS, yet early studies show that bypass signaling drives adaptive resistance …
Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition
MB Ryan, F Fece de la Cruz, S Phat, DT Myers… - Clinical cancer …, 2020 - AACR
Purpose: Although KRAS represents the most commonly mutated oncogene, it has long
been considered an “undruggable” target. Novel covalent inhibitors selective for the …
been considered an “undruggable” target. Novel covalent inhibitors selective for the …
[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 …
cancer, yet for 40 years it remained an elusive therapeutic target. Recently, allosteric …
[HTML][HTML] Targeting KRAS: the elephant in the room of epithelial cancers
V Merz, M Gaule, C Zecchetto, A Cavaliere… - Frontiers in …, 2021 - frontiersin.org
Mutations of the proto-oncogene KRAS are the most frequent gain-of-function alterations
found in cancer. KRAS is mutated in about 30% of all human tumors, but it could reach more …
found in cancer. KRAS is mutated in about 30% of all human tumors, but it could reach more …
[HTML][HTML] How to manage KRAS G12C-mutated advanced non-small-cell lung cancer
B Ricciuti, A Mira, E Andrini, P Scaparone… - Drugs in …, 2022 - ncbi.nlm.nih.gov
Constitutive KRAS signalling drives tumorigenesis across several cancer types. In non-small-
cell lung cancer (NSCLC) activating KRAS mutations occur in~ 30% of cases, and the …
cell lung cancer (NSCLC) activating KRAS mutations occur in~ 30% of cases, and the …
Resistance looms for KRAS G12C inhibitors and rational tackling strategies
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 …
efforts have witnessed a revolutionary strategy for KRAS G12C inhibitors with exhibiting …