What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past
Abstract Indoleamine 2,3-dioxygenase 1 (IDO1), a monomeric heme-containing enzyme, catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism, which plays an important role in immunity and neuronal function. Its implication in different pathophysiologic processes i...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-01847-4 |
| _version_ | 1818610201099501568 |
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| author | Yu Yao Heng Liang Xin Fang Shengnan Zhang Zikang Xing Lei Shi Chunxiang Kuang Barbara Seliger Qing Yang |
| author_facet | Yu Yao Heng Liang Xin Fang Shengnan Zhang Zikang Xing Lei Shi Chunxiang Kuang Barbara Seliger Qing Yang |
| author_sort | Yu Yao |
| collection | DOAJ |
| description | Abstract Indoleamine 2,3-dioxygenase 1 (IDO1), a monomeric heme-containing enzyme, catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism, which plays an important role in immunity and neuronal function. Its implication in different pathophysiologic processes including cancer and neurodegenerative diseases has inspired the development of IDO1 inhibitors in the past decades. However, the negative results of the phase III clinical trial of the would-be first-in-class IDO1 inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in patients with advanced malignant melanoma call for a better understanding of the role of IDO1 inhibition. In this review, the current status of the clinical development of IDO1 inhibitors will be introduced and the key pre-clinical and clinical data of epacadostat will be summarized. Moreover, based on the cautionary notes obtained from the clinical readout of epacadostat, strategies for the identification of reliable predictive biomarkers and pharmacodynamic markers as well as for the selection of the tumor types to be treated with IDO1inhibitors will be discussed. |
| first_indexed | 2024-12-16T15:10:40Z |
| format | Article |
| id | doaj.art-68d18ef741b2475db47ac95348b8d12b |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-16T15:10:40Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-68d18ef741b2475db47ac95348b8d12b2022-12-21T22:26:58ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-02-0140111410.1186/s13046-021-01847-4What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the pastYu Yao0Heng Liang1Xin Fang2Shengnan Zhang3Zikang Xing4Lei Shi5Chunxiang Kuang6Barbara Seliger7Qing Yang8State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan UniversityState Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan UniversityState Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan UniversityState Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan UniversityState Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan UniversityState Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan UniversityShanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji UniversityInstitute of Medical Immunology, Martin Luther University Halle-WittenbergState Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan UniversityAbstract Indoleamine 2,3-dioxygenase 1 (IDO1), a monomeric heme-containing enzyme, catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism, which plays an important role in immunity and neuronal function. Its implication in different pathophysiologic processes including cancer and neurodegenerative diseases has inspired the development of IDO1 inhibitors in the past decades. However, the negative results of the phase III clinical trial of the would-be first-in-class IDO1 inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in patients with advanced malignant melanoma call for a better understanding of the role of IDO1 inhibition. In this review, the current status of the clinical development of IDO1 inhibitors will be introduced and the key pre-clinical and clinical data of epacadostat will be summarized. Moreover, based on the cautionary notes obtained from the clinical readout of epacadostat, strategies for the identification of reliable predictive biomarkers and pharmacodynamic markers as well as for the selection of the tumor types to be treated with IDO1inhibitors will be discussed.https://doi.org/10.1186/s13046-021-01847-4Indoleamine 2,3-dioxygenase 1Indoleamine 2,3-dioxygenase 1 inhibitorEpacadostatTryptophan 2,3-dioxygenaseCancer immunotherapyImmune checkpoint |
| spellingShingle | Yu Yao Heng Liang Xin Fang Shengnan Zhang Zikang Xing Lei Shi Chunxiang Kuang Barbara Seliger Qing Yang What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past Journal of Experimental & Clinical Cancer Research Indoleamine 2,3-dioxygenase 1 Indoleamine 2,3-dioxygenase 1 inhibitor Epacadostat Tryptophan 2,3-dioxygenase Cancer immunotherapy Immune checkpoint |
| title | What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past |
| title_full | What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past |
| title_fullStr | What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past |
| title_full_unstemmed | What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past |
| title_short | What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past |
| title_sort | what is the prospect of indoleamine 2 3 dioxygenase 1 inhibition in cancer extrapolation from the past |
| topic | Indoleamine 2,3-dioxygenase 1 Indoleamine 2,3-dioxygenase 1 inhibitor Epacadostat Tryptophan 2,3-dioxygenase Cancer immunotherapy Immune checkpoint |
| url | https://doi.org/10.1186/s13046-021-01847-4 |
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