A highly efficient modality to block the degradation of tryptophan for cancer immunotherapy: locked nucleic acid-modified antisense oligonucleotides to inhibit human indoleamine 2,3-dioxygenase 1/tryptophan 2,3-dioxygenase expression.
Microtubule inhibitors containing immunostimulatory agents promote cancer immunochemotherapy by inhibiting tubulin polymerization and tryptophan-2,3-dioxygenase.
Despite the challenges in their discovery, the search for TDO2 inhibitors is a very active area of research, as such molecules may prove to be of great interest in not only cancer immunotherapy drug arsenal, but also in neurodegenerative diseases.
Imbalances in Trp metabolism in disorders ranging from cancer to neurodegenerative disease have stimulated interest in therapeutically targeting the KP, particularly the main rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan-2,3-dioxygenase (TDO) as well as kynurenine monooxygenase (KMO).
We review recent progress and future perspectives in targeting the IDO1/TDO2-KYN-AhR signaling pathway for the development of novel cancer immunotherapies.
Finally, this review is also directed toward assessing whether IDO and TDO are potential therapeutic target in depression associated with other diseases such as diabetes and/or cancer, as well as the development of potent IDO and TDO inhibitors.
Finally, we also provide our viewpoint regarding the future developmental directions of TDO in cancer research, especially in relation to the development and application of TDO inhibitors as novel cancer treatments.