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Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives
Since accelerated metabolism produces much higher levels of reactive oxygen species (ROS) in cancer cells compared to ROS levels found in normal cells, human MutT homolog 1 (MTH1), which sanitizes oxidized nucleotide pools, was recently demonstrated to be crucial for the survival of cancer cells, bu...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745060/ https://www.ncbi.nlm.nih.gov/pubmed/33354500 http://dx.doi.org/10.1016/j.apsb.2020.02.012 |
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author | Yin, Yizhen Chen, Fener |
author_facet | Yin, Yizhen Chen, Fener |
author_sort | Yin, Yizhen |
collection | PubMed |
description | Since accelerated metabolism produces much higher levels of reactive oxygen species (ROS) in cancer cells compared to ROS levels found in normal cells, human MutT homolog 1 (MTH1), which sanitizes oxidized nucleotide pools, was recently demonstrated to be crucial for the survival of cancer cells, but not required for the proliferation of normal cells. Therefore, dozens of MTH1 inhibitors have been developed with the aim of suppressing cancer growth by accumulating oxidative damage in cancer cells. While several inhibitors were indeed confirmed to be effective, some inhibitors failed to kill cancer cells, complicating MTH1 as a viable target for cancer eradication. In this review, we summarize the current status of developing MTH1 inhibitors as drug candidates, classify the MTH1 inhibitors based on their structures, and offer our perspectives toward the therapeutic potential against cancer through the targeting of MTH1. |
format | Online Article Text |
id | pubmed-7745060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-77450602020-12-21 Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives Yin, Yizhen Chen, Fener Acta Pharm Sin B Review Since accelerated metabolism produces much higher levels of reactive oxygen species (ROS) in cancer cells compared to ROS levels found in normal cells, human MutT homolog 1 (MTH1), which sanitizes oxidized nucleotide pools, was recently demonstrated to be crucial for the survival of cancer cells, but not required for the proliferation of normal cells. Therefore, dozens of MTH1 inhibitors have been developed with the aim of suppressing cancer growth by accumulating oxidative damage in cancer cells. While several inhibitors were indeed confirmed to be effective, some inhibitors failed to kill cancer cells, complicating MTH1 as a viable target for cancer eradication. In this review, we summarize the current status of developing MTH1 inhibitors as drug candidates, classify the MTH1 inhibitors based on their structures, and offer our perspectives toward the therapeutic potential against cancer through the targeting of MTH1. Elsevier 2020-12 2020-03-30 /pmc/articles/PMC7745060/ /pubmed/33354500 http://dx.doi.org/10.1016/j.apsb.2020.02.012 Text en © 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Review Yin, Yizhen Chen, Fener Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives |
title | Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives |
title_full | Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives |
title_fullStr | Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives |
title_full_unstemmed | Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives |
title_short | Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives |
title_sort | targeting human mutt homolog 1 (mth1) for cancer eradication: current progress and perspectives |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745060/ https://www.ncbi.nlm.nih.gov/pubmed/33354500 http://dx.doi.org/10.1016/j.apsb.2020.02.012 |
work_keys_str_mv | AT yinyizhen targetinghumanmutthomolog1mth1forcancereradicationcurrentprogressandperspectives AT chenfener targetinghumanmutthomolog1mth1forcancereradicationcurrentprogressandperspectives |