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Targeting ADAM10 in Cancer and Autoimmunity
Generating inhibitors for A Disintegrin And Metalloproteinase 10 (ADAM10), a zinc-dependent protease, was heavily invested in by the pharmaceutical industry starting over 20 years ago. There has been much enthusiasm in basic research for these inhibitors, with a multitude of studies generating signi...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105615/ https://www.ncbi.nlm.nih.gov/pubmed/32265938 http://dx.doi.org/10.3389/fimmu.2020.00499 |
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author | Smith, Timothy M. Tharakan, Anuj Martin, Rebecca K. |
author_facet | Smith, Timothy M. Tharakan, Anuj Martin, Rebecca K. |
author_sort | Smith, Timothy M. |
collection | PubMed |
description | Generating inhibitors for A Disintegrin And Metalloproteinase 10 (ADAM10), a zinc-dependent protease, was heavily invested in by the pharmaceutical industry starting over 20 years ago. There has been much enthusiasm in basic research for these inhibitors, with a multitude of studies generating significant data, yet the clinical trials have not replicated the same results. ADAM10 is ubiquitously expressed and cleaves many important substrates such as Notch, PD-L1, EGFR/HER ligands, ICOS-L, TACI, and the “stress related molecules” MIC-A, MIC-B and ULBPs. This review goes through the most recent pre-clinical data with inhibitors as well as clinical data supporting the use of ADAM10 inhibitor use in cancer and autoimmunity. It additionally addresses how ADAM10 inhibitor therapy can be improved and if inhibitor therapy can be paired with other drug treatments to maximize effectiveness in various disease states. Finally, it examines the ADAM10 substrates that are important to each disease state and if any of these substrates or ADAM10 itself is a potential biomarker for disease. |
format | Online Article Text |
id | pubmed-7105615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71056152020-04-07 Targeting ADAM10 in Cancer and Autoimmunity Smith, Timothy M. Tharakan, Anuj Martin, Rebecca K. Front Immunol Immunology Generating inhibitors for A Disintegrin And Metalloproteinase 10 (ADAM10), a zinc-dependent protease, was heavily invested in by the pharmaceutical industry starting over 20 years ago. There has been much enthusiasm in basic research for these inhibitors, with a multitude of studies generating significant data, yet the clinical trials have not replicated the same results. ADAM10 is ubiquitously expressed and cleaves many important substrates such as Notch, PD-L1, EGFR/HER ligands, ICOS-L, TACI, and the “stress related molecules” MIC-A, MIC-B and ULBPs. This review goes through the most recent pre-clinical data with inhibitors as well as clinical data supporting the use of ADAM10 inhibitor use in cancer and autoimmunity. It additionally addresses how ADAM10 inhibitor therapy can be improved and if inhibitor therapy can be paired with other drug treatments to maximize effectiveness in various disease states. Finally, it examines the ADAM10 substrates that are important to each disease state and if any of these substrates or ADAM10 itself is a potential biomarker for disease. Frontiers Media S.A. 2020-03-24 /pmc/articles/PMC7105615/ /pubmed/32265938 http://dx.doi.org/10.3389/fimmu.2020.00499 Text en Copyright © 2020 Smith, Tharakan and Martin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Smith, Timothy M. Tharakan, Anuj Martin, Rebecca K. Targeting ADAM10 in Cancer and Autoimmunity |
title | Targeting ADAM10 in Cancer and Autoimmunity |
title_full | Targeting ADAM10 in Cancer and Autoimmunity |
title_fullStr | Targeting ADAM10 in Cancer and Autoimmunity |
title_full_unstemmed | Targeting ADAM10 in Cancer and Autoimmunity |
title_short | Targeting ADAM10 in Cancer and Autoimmunity |
title_sort | targeting adam10 in cancer and autoimmunity |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105615/ https://www.ncbi.nlm.nih.gov/pubmed/32265938 http://dx.doi.org/10.3389/fimmu.2020.00499 |
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