Drug resistance

Internal medicine

Tumor microenvironment

Colorectal cancer

Monoclonal antibody

Bioinformatics

Biology

Microbiology

Gene

Cancer

Oncology

Allele

Antibody

Immunology

Antibody-drug conjugate

Microsatellite instability

Targeted therapy

Drug

Cancer research

Biochemistry

Microsatellite

Medicine

Pharmacology

World Journal of Gastroenterology

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 antibodydrug 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.

Drug resistance and new therapies in colorectal cancer