The Promising Future of IDO and TDO Inhibitors as Immunotherapeutic Agents in Cancer Treatment: Role, Challenge and Implication

Raed M Al-Zoubi^1*Mai Elaarag¹Ahmad R. Al-Qudimat¹Enas A. Al-Hurani²Zainab Feras¹Ala’a Farhan¹Sally R. Al-Zoubi³Abbas Khan⁴Abdelali Agouni⁴Mohanad Shkoor⁴Hiba Bawadi⁴Zain Z. Zakaria⁴Mazhar Salim Al Zoubi⁵Khalid Alrumaihi¹

• ¹Hamad Medical Corporation, Doha, Qatar
• ²Zarqa University, Zarqa, Zarqa, Jordan
• ³Jordan University of Science and Technology, Irbid, Irbid, Jordan
• ⁴Qatar University, Doha, Qatar
• ⁵Yarmouk University, Irbid, Irbid, Jordan

Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) inhibitors are promising avenues in cancer immunotherapy. These enzymes are important in the kynurenine pathway because they modulate immune responses and allow malignancies to evade the immune system. Therapeutic therapies that target IDO and TDO attempt to improve immune surveillance and anticancer activity. This review looks at the mechanisms of IDO/TDO in cancer etiology, their consequences in the tumor microenvironment, and the therapeutic development of inhibitors currently being studied. Among these, medications like Indoximod, Epacadostat, and Navoximod have shown promise in influencing the immune system and slowing tumor progression, whilst dual inhibitors like HTI-1090 try to address broader metabolic connections. Despite tremendous progress, obstacles like tumor heterogeneity, off-target consequences, and varying patient responses remain. The use of IDO/TDO inhibitors with conventional medicines demonstrates their potential to change cancer treatment, subject to more research to maximize efficacy and safety.