Simulating and predicting cellular and in vivo responses of colon cancer to combined treatment with chemotherapy and IAP antagonist Birinapant/TL32711.

ABSTRACT: Apoptosis resistance contributes to treatment failure in colorectal cancer (CRC). New treatments that reinstate apoptosis competency have potential to improve patient outcome but require predictive biomarkers to target them to responsive patient populations. Inhibitor of apoptosis proteins (IAPs) suppress apoptosis, contributing to drug resistance; IAP antagonists such as TL32711 have therefore been developed. We developed a systems biology approach for predicting response of CRC cells to chemotherapy and TL32711 combinations in vitro and in vivo. CRC cells responded poorly to TL32711 monotherapy in vitro; however, co-treatment with 5-fluorouracil (5-FU) and oxaliplatin enhanced TL32711-induced apoptosis. Notably, cells from genetically identical populations responded highly heterogeneousl

SUBMITTER: Crawford N 

PROVIDER: S-EPMC5989936 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature