[HTML][HTML] Drug resistance and new therapies in colorectal cancer

K Van der Jeught, HC Xu, YJ Li, XB Lu… - World journal of …, 2018 - ncbi.nlm.nih.gov
K Van der Jeught, HC Xu, YJ Li, XB Lu, G Ji
World journal of gastroenterology, 2018ncbi.nlm.nih.gov
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 …
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.
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