publication . Article . Other literature type . 2017

A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

Channing Der;
Open Access
  • Published: 01 Jul 2017 Journal: Cell Reports, volume 20, pages 999-1,015 (issn: 2211-1247, Copyright policy)
  • Publisher: Elsevier BV
Abstract
Summary Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription. Furthermore, these sc...
Subjects
free text keywords: General Biochemistry, Genetics and Molecular Biology, Cell cycle, Biology, Synthetic lethality, Genetics, MAPK/ERK pathway, Effector, Mutant, Cancer research, PI3K/AKT/mTOR pathway, KRAS, medicine.disease_cause, medicine, Signal transduction, Article, CRISPR/Cas9, pooled screening, PIK3CA, SRC, BIM, apoptosis, drug resistance, Biology (General), QH301-705.5
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publication . Article . Other literature type . 2017

A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

Channing Der;