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 …

Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer

KL Bryant, CA Stalnecker, D Zeitouni, JE Klomp… - Nature medicine, 2019 - nature.com
Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS-and autophagy-
dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been …

Atypical KRASG12R Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer

GA Hobbs, NM Baker, AM Miermont, RD Thurman… - Cancer discovery, 2020 - AACR
Allele-specific signaling by different KRAS alleles remains poorly understood. The KRAS
G12R mutation displays uneven prevalence among cancers that harbor the highest …

The KRASG12C Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy

DM Briere, S Li, A Calinisan, N Sudhakar… - Molecular cancer …, 2021 - AACR
Abstract KRASG12C inhibitors, including MRTX849, are promising treatment options for
KRAS-mutant non–small cell lung cancer (NSCLC). PD-1 inhibitors are approved in NSCLC; …

Functional and biological heterogeneity of KRASQ61 mutations

MV Huynh, GA Hobbs, A Schaefer, M Pierobon… - Science …, 2022 - science.org
Missense mutations at the three hotspots in the guanosine triphosphatase (GTPase) RAS—
Gly12, Gly13, and Gln61 (commonly known as G12, G13, and Q61, respectively)—occur …

[HTML][HTML] Low-dose vertical inhibition of the RAF-MEK-ERK cascade causes apoptotic death of KRAS mutant cancers

I Ozkan-Dagliyan, JN Diehl, SD George, A Schaefer… - Cell reports, 2020 - cell.com
We address whether combinations with a pan-RAF inhibitor (RAFi) would be effective in
KRAS mutant pancreatic ductal adenocarcinoma (PDAC). Chemical library and CRISPR …

RHOAL57V drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling

A Schaefer, RG Hodge, H Zhang, GA Hobbs, J Dilly… - Science …, 2023 - science.org
Cancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at
different locations from the mutational hotspots in the structurally and biochemically related …

Integrated multi-omics analyses on patient-derived CRC organoids highlight altered molecular pathways in colorectal cancer progression involving PTEN

M Codrich, E Dalla, C Mio, G Antoniali… - Journal of Experimental …, 2021 - Springer
Background Colorectal cancer (CRC) represents the fourth leading cause of cancer-related
deaths. The heterogeneity of CRC identity limits the usage of cell lines to study this type of …

Extensive three-dimensional intratumor proteomic heterogeneity revealed by multiregion sampling in high-grade serous ovarian tumor specimens

AL Hunt, NW Bateman, W Barakat, S Makohon-Moore… - Iscience, 2021 - cell.com
Enriched tumor epithelium, tumor-associated stroma, and whole tissue were collected by
laser microdissection from thin sections across spatially separated levels of ten high-grade …

Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling

AL Hunt, NW Bateman, W Barakat… - Clinical proteomics, 2024 - Springer
Background Although uterine serous carcinoma (USC) represents a small proportion of all
uterine cancer cases, patients with this aggressive subtype typically have high rates of …