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This content will become publicly available on March 5, 2019

Title: New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling

RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisition of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [2]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Univ. College Dublin (United Kingdom)
  3. Northern Arizona Univ., Flagstaff, AZ (United States)
  4. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico Comprehensive Cancer Center, Albuquerque, NM (United States)
Publication Date:
Report Number(s):
LA-UR-17-31291
Journal ID: ISSN 1044-579X
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Seminars in Cancer Biology
Additional Journal Information:
Journal Name: Seminars in Cancer Biology; Journal ID: ISSN 1044-579X
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological Science
OSTI Identifier:
1425769