Abstract
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 α-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.
Original language | English (US) |
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Pages (from-to) | 3834-3848 |
Number of pages | 15 |
Journal | World journal of gastroenterology |
Volume | 24 |
Issue number | 34 |
DOIs | |
State | Published - Sep 14 2018 |
Keywords
- Antibody-drug conjugates
- Checkpoint inhibitors
- Colorectal cancer
- Immunotherapy
- Microbiome
- Therapy resistance
- Tumor microenvironment
- Α-amanitin
ASJC Scopus subject areas
- Gastroenterology