publication . Other literature type . Article . 2017

A landscape of therapeutic cooperativity in KRAS mutant cancers reveals principles for controlling tumor evolution

Grace R. Anderson; Peter S. Winter; Kevin H. Lin; Daniel P. Nussbaum; Merve Cakir; Elizabeth M. Stein; Ryan S. Soderquist; Lorin Crawford; Jim C. Leeds; Rachel Newcomb; ...
Open Access English
  • Published: 01 Jul 2017
Abstract
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 screens re...
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Medical Subject Headings: neoplasms
free text keywords: Article, General Biochemistry, Genetics and Molecular Biology, CRISPR/Cas9, pooled screening, PIK3CA, SRC, BIM, apoptosis, drug resistance, Signal transduction, Effector, KRAS, medicine.disease_cause, medicine, Biology, Synthetic lethality, MAPK/ERK pathway, Mutant, Cell cycle, Cancer research, PI3K/AKT/mTOR pathway, lcsh:Biology (General), lcsh:QH301-705.5
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