Heterogeneity, drug resistance and clonal evolution of colorectal cancers

Alberto Bardelli1

1University of Toringo, Turin, Italy

Abstract

Colorectal cancers evolve by a reiterative process of genetic diversification and clonal evolution. Tissue and liquid biopsies can be used to define CRC molecular subtypes and to monitor clonal evolution during therapy. Using these approaches, CRC patients were found to respond selectively to targeted agents interfering with oncogenic nodes of the EGFR signalling pathway. Notably, the patient-specific responses can be recapitulated and paralleled in cellular and mouse clinical proxies (CRC-avatars). The inevitable development of acquired resistance to inhibitors of the EGFR signalling axis presently limits further clinical advances. Strategies to prevent or overcome resistance are therefore essential to design the next generation of molecularly-driven clinical trials for CRC patients.