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Drug resistance and new therapies in colorectal cancer.

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 ?-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.

SUBMITTER: Van der Jeught K

PROVIDER: S-EPMC6141340 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Drug resistance and new therapies in colorectal cancer.

Van der Jeught Kevin K Xu Han-Chen HC Li Yu-Jing YJ Lu Xiong-Bin XB Ji Guang G

World journal of gastroenterology 20180901 34

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 ...[more]

PMID: 30228778

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