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PERSPECTIVE article

Front. Oncol.
Sec. Cancer Metabolism
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1524651
This article is part of the Research Topic Metabolic Crosstalk between Cancer Cells and Immune Cells in the Tumor Microenvironment: Cellular and Molecular Insights, and their Therapeutic Implications View all 10 articles

Targeting the Kynurenine Pathway: Another Therapeutic Opportunity in the Metabolic Crosstalk between Cancer and Immune Cells

Provisionally accepted
Medhi Wangpaichitr Medhi Wangpaichitr 1,2,3*George Theodoropoulos George Theodoropoulos 1Irene Kang Irene Kang 1
  • 1 Miami VA Healthcare System, Veterans Health Administration, United States Department of Veterans Affairs, Miami, United States
  • 2 DeWitt Daughtry Family Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States
  • 3 Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, United States

The final, formatted version of the article will be published soon.

    The pivotal role of metabolic reprogramming in cancer-related drug resistance, through the tryptophan-catabolized kynurenine pathway (KP), has been particularly underscored in recent research. This pathway, driven by indoleamine 2,3-dioxygenase 1 (IDO1), facilitates immune evasion and promotes tumor progression by fostering an immunosuppressive environment. In Phase III investigation of the combination of IDO1 inhibition with immune checkpoint inhibitors (ICIs), the combination therapy was not efficacious. In this review, we revisit current advances, explore future directions, and emphasize the importance of dual inhibition of the KP rate-limiting enzymes IDO1 and tryptophan 2,3-dioxygenase-2 (TDO2) in appropriate patient populations. We propose that dual inhibition may maximize the therapeutic potential of KP inhibition. Additionally, we delve into the complex cellular interactions in cancer and metabolic dependencies within the tumor microenvironment (TME). Insights from preclinical studies, recent clinical trials, and promising therapeutic combinations will be discussed to elucidate and promote a clear path forward for the direction of KP research into cancer-related outcomes.

    Keywords: lung cancer, Metabolism, Immunometabolism, Drug Resistance, Kynurenine, DUAL INHIBITORS

    Received: 08 Nov 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Wangpaichitr, Theodoropoulos and Kang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Medhi Wangpaichitr, Miami VA Healthcare System, Veterans Health Administration, United States Department of Veterans Affairs, Miami, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.