RAS-targeted therapies: is the undruggable drugged?

AR Moore, SC Rosenberg, F McCormick… - Nature reviews Drug …, 2020 - nature.com
Abstract RAS (KRAS, NRAS and HRAS) is the most frequently mutated gene family in
cancers, and, consequently, investigators have sought an effective RAS inhibitor for more …

Targeting KRAS mutant cancers: from druggable therapy to drug resistance

C Zhu, X Guan, X Zhang, X Luan, Z Song, X Cheng… - Molecular cancer, 2022 - Springer
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 …

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 …

Copper bioavailability is a KRAS-specific vulnerability in colorectal cancer

L Aubert, N Nandagopal, Z Steinhart, G Lavoie… - Nature …, 2020 - nature.com
Despite its importance in human cancers, including colorectal cancers (CRC), oncogenic
KRAS has been extremely challenging to target therapeutically. To identify potential …

High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response

H Gao, JM Korn, S Ferretti, JE Monahan, Y Wang… - Nature medicine, 2015 - nature.com
Profiling candidate therapeutics with limited cancer models during preclinical development
hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous …

KRAS drives immune evasion in a genetic model of pancreatic cancer

I Ischenko, S D'Amico, M Rao, J Li, MJ Hayman… - Nature …, 2021 - nature.com
Immune evasion is a hallmark of KRAS-driven cancers, but the underlying causes remain
unresolved. Here, we use a mouse model of pancreatic ductal adenocarcinoma to inactivate …

Epithelial-to-mesenchymal transition is a cause of both intrinsic and acquired resistance to KRAS G12C inhibitor in KRAS G12C–mutant non–small cell lung cancer

Y Adachi, K Ito, Y Hayashi, R Kimura, TZ Tan… - Clinical Cancer …, 2020 - AACR
Purpose: KRAS is among the most commonly mutated oncogene in cancer including non–
small cell lung cancer (NSCLC). In early clinical trials, inhibitors targeting G12C-mutant …

Drugging the undruggable RAS: Mission possible?

AD Cox, SW Fesik, AC Kimmelman, J Luo… - Nature reviews Drug …, 2014 - nature.com
Despite more than three decades of intensive effort, no effective pharmacological inhibitors
of the RAS oncoproteins have reached the clinic, prompting the widely held perception that …

Harnessing connectivity in a large-scale small-molecule sensitivity dataset

B Seashore-Ludlow, MG Rees, JH Cheah, M Cokol… - Cancer discovery, 2015 - AACR
Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic
agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) …

ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics

CL Arteaga, JA Engelman - Cancer cell, 2014 - cell.com
ERBB receptors were linked to human cancer pathogenesis approximately three decades
ago. Biomedical investigators have since developed substantial understanding of the …