Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer
| Autor: | David M. Alvarado, Srikanth Santhanam, Matthew A. Ciorba |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Kynurenine pathway Colon Colorectal cancer medicine.medical_treatment Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Physiology (medical) medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Gastrointestinal cancer Kynurenine PI3K/AKT/mTOR pathway Gastrointestinal Neoplasms Inflammation Biochemistry (medical) Tryptophan Public Health Environmental and Occupational Health Cancer General Medicine Immunotherapy medicine.disease 030104 developmental biology chemistry Immunology Cancer research Signal Transduction 030215 immunology |
| Zdroj: | Translational Research. 167:67-79 |
| ISSN: | 1931-5244 |
| DOI: | 10.1016/j.trsl.2015.07.003 |
| Popis: | Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death in the United States. Cytotoxic therapies cause significant side effects for most patients and do not offer cure in many advanced cases of CRC. Immunotherapies are a promising new approach to harness the body’s own immune system and inflammatory response to attack and clear the cancer. Tryptophan metabolism along the kynurenine pathway is a particularly promising target for immunotherapy. Indoleamine 2,3 dioxygenase 1 (IDO1) is the most well studied of the enzymes that initiate this pathway and it is commonly overexpressed in CRC. Herein, we provide an in-depth review of how tryptophan metabolism and kynurenine pathway metabolites shape factors important to CRC pathogenesis including the host mucosal immune system, pivotal transcriptional pathways of neoplastic growth and luminal microbiota. This pathway’s role in other gastrointestinal malignancies such as gastric, pancreatic, esophageal and gastrointestinal stromal tumors (GIST) is also discussed. Finally, we highlight how currently available small molecule inhibitors and emerging methods for therapeutic targeting of IDO1 might be applied to colon, rectal and colitis associated cancer. |
| Databáze: | OpenAIRE |
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