Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures.

ABSTRACT: Organoid cultures derived from colorectal cancer (CRC) samples are increasingly used as preclinical models for studying tumor biology and the effects of targeted therapies under conditions capturing in vitro the genetic make-up of heterogeneous and even individual neoplasms. While 3D cultures are initiated from surgical specimens comprising multiple cell populations, the impact of tumor heterogeneity on drug effects in organoid cultures has not been addressed systematically. Here we have used a cohort of well-characterized CRC organoids to study the influence of tumor heterogeneity on the activity of the KRAS/MAPK-signaling pathway and the consequences of treatment by inhibitors targeting EGFR and downstream effectors. MAPK signaling, analyzed by targeted proteomics, shows unexpected heter

SUBMITTER: Schumacher D 

PROVIDER: S-EPMC6457557 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature