The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated
The kynurenine pathway has been highlighted as a gatekeeper of immune-privileged sites through its ability to generate from tryptophan a set of immunosuppressive metabolic intermediates. It additionally constitutes an important source of cellular NAD<sup>+</sup> for the organism. Hijacki...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/11/2793 |
| _version_ | 1797493856054280192 |
|---|---|
| author | Roumaïssa Gouasmi Carole Ferraro-Peyret Stéphane Nancey Isabelle Coste Toufic Renno Cédric Chaveroux Nicolas Aznar Stéphane Ansieau |
| author_facet | Roumaïssa Gouasmi Carole Ferraro-Peyret Stéphane Nancey Isabelle Coste Toufic Renno Cédric Chaveroux Nicolas Aznar Stéphane Ansieau |
| author_sort | Roumaïssa Gouasmi |
| collection | DOAJ |
| description | The kynurenine pathway has been highlighted as a gatekeeper of immune-privileged sites through its ability to generate from tryptophan a set of immunosuppressive metabolic intermediates. It additionally constitutes an important source of cellular NAD<sup>+</sup> for the organism. Hijacking of its immunosuppressive functions, as recurrently observed in multiple cancers, facilitates immune evasion and promotes tumor development. Based on these observations, researchers have focused on characterizing indoleamine 2,3-dioxygenase (IDO1), the main enzyme catalyzing the first and limiting step of the pathway, and on developing therapies targeting it. Unfortunately, clinical trials studying IDO1 inhibitors have thus far not met expectations, highlighting the need to unravel this complex signaling pathway further. Recent advances demonstrate that these metabolites additionally promote tumor growth, metastatic dissemination and chemoresistance by a combination of paracrine and autocrine effects. Production of NAD<sup>+</sup> also contributes to cancer progression by providing cancer cells with enhanced plasticity, invasive properties and chemoresistance. A comprehensive survey of this complexity is challenging but necessary to achieve medical success. |
| first_indexed | 2024-03-10T01:25:58Z |
| format | Article |
| id | doaj.art-82c2f5b6827a4338a23c4fd16c51a458 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T01:25:58Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-82c2f5b6827a4338a23c4fd16c51a4582023-11-23T13:51:12ZengMDPI AGCancers2072-66942022-06-011411279310.3390/cancers14112793The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It ComplicatedRoumaïssa Gouasmi0Carole Ferraro-Peyret1Stéphane Nancey2Isabelle Coste3Toufic Renno4Cédric Chaveroux5Nicolas Aznar6Stéphane Ansieau7Centre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université Lyon 1, Université de Lyon, 69373 Lyon, FranceCentre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université Lyon 1, Université de Lyon, 69373 Lyon, FranceDepartment of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre Bénite, France and INSERM U1111—CIRI, 69365 Lyon, FranceCentre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université Lyon 1, Université de Lyon, 69373 Lyon, FranceCentre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université Lyon 1, Université de Lyon, 69373 Lyon, FranceCentre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université Lyon 1, Université de Lyon, 69373 Lyon, FranceCentre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université Lyon 1, Université de Lyon, 69373 Lyon, FranceCentre de Recherche en Cancérologie de Lyon, CNRS UMR5286, Inserm U1052, Université Lyon 1, Université de Lyon, 69373 Lyon, FranceThe kynurenine pathway has been highlighted as a gatekeeper of immune-privileged sites through its ability to generate from tryptophan a set of immunosuppressive metabolic intermediates. It additionally constitutes an important source of cellular NAD<sup>+</sup> for the organism. Hijacking of its immunosuppressive functions, as recurrently observed in multiple cancers, facilitates immune evasion and promotes tumor development. Based on these observations, researchers have focused on characterizing indoleamine 2,3-dioxygenase (IDO1), the main enzyme catalyzing the first and limiting step of the pathway, and on developing therapies targeting it. Unfortunately, clinical trials studying IDO1 inhibitors have thus far not met expectations, highlighting the need to unravel this complex signaling pathway further. Recent advances demonstrate that these metabolites additionally promote tumor growth, metastatic dissemination and chemoresistance by a combination of paracrine and autocrine effects. Production of NAD<sup>+</sup> also contributes to cancer progression by providing cancer cells with enhanced plasticity, invasive properties and chemoresistance. A comprehensive survey of this complexity is challenging but necessary to achieve medical success.https://www.mdpi.com/2072-6694/14/11/2793NADkynureninetumor initiation and progression |
| spellingShingle | Roumaïssa Gouasmi Carole Ferraro-Peyret Stéphane Nancey Isabelle Coste Toufic Renno Cédric Chaveroux Nicolas Aznar Stéphane Ansieau The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated Cancers NAD kynurenine tumor initiation and progression |
| title | The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated |
| title_full | The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated |
| title_fullStr | The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated |
| title_full_unstemmed | The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated |
| title_short | The Kynurenine Pathway and Cancer: Why Keep It Simple When You Can Make It Complicated |
| title_sort | kynurenine pathway and cancer why keep it simple when you can make it complicated |
| topic | NAD kynurenine tumor initiation and progression |
| url | https://www.mdpi.com/2072-6694/14/11/2793 |
| work_keys_str_mv | AT roumaissagouasmi thekynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT caroleferraropeyret thekynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT stephanenancey thekynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT isabellecoste thekynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT touficrenno thekynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT cedricchaveroux thekynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT nicolasaznar thekynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT stephaneansieau thekynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT roumaissagouasmi kynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT caroleferraropeyret kynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT stephanenancey kynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT isabellecoste kynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT touficrenno kynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT cedricchaveroux kynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT nicolasaznar kynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated AT stephaneansieau kynureninepathwayandcancerwhykeepitsimplewhenyoucanmakeitcomplicated |