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An Enolase Inhibitor for the Targeted Treatment of ENO1-Deleted Cancers
Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We previously identified a subset of cancers harboring homozygous deletion of the glycolytic enzyme Enolase (ENO1) with exceptional sensitivity to inhibition of its redundant paralogue, ENO2, through a therapeutic st...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744354/ https://www.ncbi.nlm.nih.gov/pubmed/33230295 http://dx.doi.org/10.1038/s42255-020-00313-3 |
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| author | Lin, Yu-Hsi Satani, Nikunj Hammoudi, Naima Yan, Victoria C. Barekatain, Yasaman Khadka, Sunada Ackroyd, Jeffrey J. Georgiou, Dimitra K. Pham, Cong-Dat Arthur, Kenisha Maxwell, David Peng, Zhenghong Leonard, Paul G. Czako, Barbara Pisaneschi, Federica Mandal, Pijus Sun, Yuting Zielinski, Rafal Pando, Susana Castro Wang, Xiaobo Tran, Theresa Xu, Quanyu Wu, Qi Jiang, Yongying Kang, Zhijun Asara, John M. Priebe, Waldemar Bornmann, William Marszalek, Joseph R. DePinho, Ronald A. Muller, Florian L. |
| author_facet | Lin, Yu-Hsi Satani, Nikunj Hammoudi, Naima Yan, Victoria C. Barekatain, Yasaman Khadka, Sunada Ackroyd, Jeffrey J. Georgiou, Dimitra K. Pham, Cong-Dat Arthur, Kenisha Maxwell, David Peng, Zhenghong Leonard, Paul G. Czako, Barbara Pisaneschi, Federica Mandal, Pijus Sun, Yuting Zielinski, Rafal Pando, Susana Castro Wang, Xiaobo Tran, Theresa Xu, Quanyu Wu, Qi Jiang, Yongying Kang, Zhijun Asara, John M. Priebe, Waldemar Bornmann, William Marszalek, Joseph R. DePinho, Ronald A. Muller, Florian L. |
| author_sort | Lin, Yu-Hsi |
| collection | PubMed |
| description | Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We previously identified a subset of cancers harboring homozygous deletion of the glycolytic enzyme Enolase (ENO1) with exceptional sensitivity to inhibition of its redundant paralogue, ENO2, through a therapeutic strategy known as collateral lethality. Here, we show that a small molecule Enolase inhibitor, POMHEX, can selectively kill ENO1-deleted glioma cells at low nanomolar concentrations and eradicate intracranial orthotopic ENO1-deleted tumors in mice at doses well-tolerated in non-human primates. Our data provide in vivo proof-of-principal for the power of collateral lethality in precision oncology and demonstrate the utility of POMHEX for glycolysis inhibition with potential across a range of therapeutic settings. |
| format | Online Article Text |
| id | pubmed-7744354 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-77443542021-05-23 An Enolase Inhibitor for the Targeted Treatment of ENO1-Deleted Cancers Lin, Yu-Hsi Satani, Nikunj Hammoudi, Naima Yan, Victoria C. Barekatain, Yasaman Khadka, Sunada Ackroyd, Jeffrey J. Georgiou, Dimitra K. Pham, Cong-Dat Arthur, Kenisha Maxwell, David Peng, Zhenghong Leonard, Paul G. Czako, Barbara Pisaneschi, Federica Mandal, Pijus Sun, Yuting Zielinski, Rafal Pando, Susana Castro Wang, Xiaobo Tran, Theresa Xu, Quanyu Wu, Qi Jiang, Yongying Kang, Zhijun Asara, John M. Priebe, Waldemar Bornmann, William Marszalek, Joseph R. DePinho, Ronald A. Muller, Florian L. Nat Metab Article Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We previously identified a subset of cancers harboring homozygous deletion of the glycolytic enzyme Enolase (ENO1) with exceptional sensitivity to inhibition of its redundant paralogue, ENO2, through a therapeutic strategy known as collateral lethality. Here, we show that a small molecule Enolase inhibitor, POMHEX, can selectively kill ENO1-deleted glioma cells at low nanomolar concentrations and eradicate intracranial orthotopic ENO1-deleted tumors in mice at doses well-tolerated in non-human primates. Our data provide in vivo proof-of-principal for the power of collateral lethality in precision oncology and demonstrate the utility of POMHEX for glycolysis inhibition with potential across a range of therapeutic settings. 2020-11-23 2020-12 /pmc/articles/PMC7744354/ /pubmed/33230295 http://dx.doi.org/10.1038/s42255-020-00313-3 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Lin, Yu-Hsi Satani, Nikunj Hammoudi, Naima Yan, Victoria C. Barekatain, Yasaman Khadka, Sunada Ackroyd, Jeffrey J. Georgiou, Dimitra K. Pham, Cong-Dat Arthur, Kenisha Maxwell, David Peng, Zhenghong Leonard, Paul G. Czako, Barbara Pisaneschi, Federica Mandal, Pijus Sun, Yuting Zielinski, Rafal Pando, Susana Castro Wang, Xiaobo Tran, Theresa Xu, Quanyu Wu, Qi Jiang, Yongying Kang, Zhijun Asara, John M. Priebe, Waldemar Bornmann, William Marszalek, Joseph R. DePinho, Ronald A. Muller, Florian L. An Enolase Inhibitor for the Targeted Treatment of ENO1-Deleted Cancers |
| title | An Enolase Inhibitor for the Targeted Treatment of ENO1-Deleted Cancers |
| title_full | An Enolase Inhibitor for the Targeted Treatment of ENO1-Deleted Cancers |
| title_fullStr | An Enolase Inhibitor for the Targeted Treatment of ENO1-Deleted Cancers |
| title_full_unstemmed | An Enolase Inhibitor for the Targeted Treatment of ENO1-Deleted Cancers |
| title_short | An Enolase Inhibitor for the Targeted Treatment of ENO1-Deleted Cancers |
| title_sort | enolase inhibitor for the targeted treatment of eno1-deleted cancers |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744354/ https://www.ncbi.nlm.nih.gov/pubmed/33230295 http://dx.doi.org/10.1038/s42255-020-00313-3 |
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