Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is alpha-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.
[1]Shanghai Univ Tradit Chinese Med, Inst Digest Dis, Longhua Hosp, 725 South Wanping Rd, Shanghai 200032, Peoples R China.
[2]Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[3]Indiana Univ Sch Med, Indiana Univ Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA.
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