Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer.

ABSTRACT: Utilizing molecular data to derive functional physiological models tailored for specific cancer cells can facilitate the use of individually tailored therapies. To this end we present an approach termed PRIME for generating cell-specific genome-scale metabolic models (GSMMs) based on molecular and phenotypic data. We build >280 models of normal and cancer cell-lines that successfully predict metabolic phenotypes in an individual manner. We utilize this set of cell-specific models to predict drug targets that selectively inhibit cancerous but not normal cell proliferation. The top predicted target, MLYCD, is experimentally validated and the metabolic effects of MLYCD depletion investigated. Furthermore, we tested cell-specific predicted responses to the inhibition of metabolic enzymes, and

SUBMITTER: Yizhak K 

PROVIDER: S-EPMC4238051 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature