Multiple cancers escape from multiple MAPK pathway inhibitors and use DNA replication stress signaling to tolerate aberrant cell cycles

• Published in: Science signaling Vol. 16; no. 796; p. eade8744
• Main Authors: Hoffman, Timothy E, Nangia, Varuna, Ill, C Ryland, Passanisi, Victor J, Armstrong, Claire, Yang, Chen, Spencer, Sabrina L
• Format: Journal Article
• Language: English
• Published: United States 01.08.2023
• Subjects: Cell Cycle; Cell Cycle Proteins - metabolism; Cell Line, Tumor; DNA Replication; Humans; MAP Kinase Signaling System - genetics; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins B-raf - metabolism

Many cancers harbor pro-proliferative mutations of the mitogen-activated protein kinase (MAPK) pathway. In BRAF-driven melanoma cells treated with BRAF inhibitors, subpopulations of cells escape drug-induced quiescence through a nongenetic manner of adaptation and resume slow proliferation. Here, we...