Low-Dose Vertical Inhibition of the RAF-MEK-ERK Cascade Causes Apoptotic Death of KRAS Mutant Cancers.

doi:10.1016/j.celrep.2020.107764

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Article

Low-Dose Vertical Inhibition of the RAF-MEK-ERK Cascade Causes Apoptotic Death of KRAS Mutant Cancers.

Cell reports - 16 Jun 2020

Ozkan-Dagliyan Irem, Diehl J Nathaniel, George Samuel D, Schaefer Antje, Papke Bjoern, Klotz-Noack Kathleen, Waters Andrew M, Goodwin Craig M, Gautam Prson, Pierobon Mariaelena, Peng Sen, Gilbert Thomas S K, Lin Kevin H, Dagliyan Onur, Wennerberg Krister, Petricoin Emanuel F, Tran Nhan L, Bhagwat Shripad V, Tiu Ramon V, Peng Sheng-Bin, Herring Laura E, Graves Lee M, Sers Christine, Wood Kris C, Cox Adrienne D, Der Channing J

Abstract excerpt

We address whether combinations with a pan-RAF inhibitor (RAFi) would be effective in KRAS mutant pancreatic ductal adenocarcinoma (PDAC). Chemical library and CRISPR genetic screens identify combinations causing apoptotic anti-tumor activity. The most potent combination, concurrent inhibition of RAF (RAFi) and ERK (ERKi), is highly synergistic at low doses in cell line, organoid, and rat models of PDAC, whereas...

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PMID: 32553168
DOI: 10.1016/j.celrep.2020.107764
PMCID: PMC7393480

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-08.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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