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

Erickson, Keesha E.; Rukhlenko, Oleksii S.; Posner, Richard G.; Hlavacek, William S.; Kholodenko, Boris N.

doi:10.1016/j.semcancer.2018.02.008

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

Journal Article · 05 March 2018 · Seminars in Cancer Biology

DOI: https://doi.org/10.1016/j.semcancer.2018.02.008 · OSTI ID:1425769

Erickson, Keesha E. ^[1]; Rukhlenko, Oleksii S. ^[2]; Posner, Richard G. ^[3]; Hlavacek, William S. ^[4]; Kholodenko, Boris N. ^[2]

Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Univ. College Dublin (United Kingdom)
Northern Arizona Univ., Flagstaff, AZ (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico Comprehensive Cancer Center, Albuquerque, NM (United States)

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.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1425769

Report Number(s):: LA-UR-17-31291

Journal Information:: Seminars in Cancer Biology, Vol. 54; ISSN 1044-579X

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 13 works

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