Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells
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...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1524651/full |
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| author | Irene Kang Irene Kang George Theodoropoulos Medhi Wangpaichitr Medhi Wangpaichitr Medhi Wangpaichitr Medhi Wangpaichitr |
| author_facet | Irene Kang Irene Kang George Theodoropoulos Medhi Wangpaichitr Medhi Wangpaichitr Medhi Wangpaichitr Medhi Wangpaichitr |
| author_sort | Irene Kang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b33c723ba6354b2a8ce30dd34162e990 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-b33c723ba6354b2a8ce30dd34162e9902025-01-22T05:19:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15246511524651Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cellsIrene Kang0Irene Kang1George Theodoropoulos2Medhi Wangpaichitr3Medhi Wangpaichitr4Medhi Wangpaichitr5Medhi Wangpaichitr6Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL, United StatesSouth Florida VA Foundation for Research and Education, Miami, FL, United StatesDepartment of Veterans Affairs, Miami VA Healthcare System, Miami, FL, United StatesDepartment of Veterans Affairs, Miami VA Healthcare System, Miami, FL, United StatesSouth Florida VA Foundation for Research and Education, Miami, FL, United StatesDepartment of Surgery, Division of Thoracic Surgery, University of Miami, Miami, FL, United StatesSylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2024.1524651/fulllung cancermetabolismimmunometabolismdrug resistancekynureninedual inhibitors |
| spellingShingle | Irene Kang Irene Kang George Theodoropoulos Medhi Wangpaichitr Medhi Wangpaichitr Medhi Wangpaichitr Medhi Wangpaichitr Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells Frontiers in Oncology lung cancer metabolism immunometabolism drug resistance kynurenine dual inhibitors |
| title | Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells |
| title_full | Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells |
| title_fullStr | Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells |
| title_full_unstemmed | Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells |
| title_short | Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells |
| title_sort | targeting the kynurenine pathway another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells |
| topic | lung cancer metabolism immunometabolism drug resistance kynurenine dual inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1524651/full |
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