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PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance

First-line treatments for oral cancer typically include surgery, radiation, and in some cases, chemotherapy. Radiation and oral cancer chemotherapeutics confer cytotoxicity largely by inducing DNA damage, underscoring the importance of the cellular DNA damage repair and response pathways in cancer t...

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Autores principales: Wang, Feifei, Gouttia, Odjo G., Wang, Ling, Peng, Aimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769238/
https://www.ncbi.nlm.nih.gov/pubmed/35071239
http://dx.doi.org/10.3389/fcell.2021.804962
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author Wang, Feifei
Gouttia, Odjo G.
Wang, Ling
Peng, Aimin
author_facet Wang, Feifei
Gouttia, Odjo G.
Wang, Ling
Peng, Aimin
author_sort Wang, Feifei
collection PubMed
description First-line treatments for oral cancer typically include surgery, radiation, and in some cases, chemotherapy. Radiation and oral cancer chemotherapeutics confer cytotoxicity largely by inducing DNA damage, underscoring the importance of the cellular DNA damage repair and response pathways in cancer therapy. However, tumor recurrence and acquired resistance, following the initial response to treatment, remains as a major clinical challenge. By analyzing oral tumor cells derived from the primary and recurrent tumors of the same patient, our study revealed upregulated PARP1 expression in the recurrent tumor cells. Cisplatin and 5-fluorouracil treatment further augmented PARP1 expression in the recurrent, but not the primary, tumor cells. Post-treatment upregulation of PARP1 was dependent on the catalytic activities of PARP and CDK7. Consistent with the established function of PARP1 in DNA repair, we showed that overexpression of PARP1 rendered the primary tumor cells highly resistant to DNA damage treatment. Conversely, PARP inhibition partially reversed the treatment resistance in the recurrent tumor cells; combinatorial treatment using a PARP inhibitor and cisplatin/5-fluorouracil significantly sensitized the tumor response in vivo. Taken together, we reported here PARP1 upregulation as a clinically relevant mechanism involved in oral cancer recurrence, and suggested the clinical benefit of PARP inhibitors, currently approved for the treatment of several other types of cancer, in oral cancer.
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spelling pubmed-87692382022-01-20 PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance Wang, Feifei Gouttia, Odjo G. Wang, Ling Peng, Aimin Front Cell Dev Biol Cell and Developmental Biology First-line treatments for oral cancer typically include surgery, radiation, and in some cases, chemotherapy. Radiation and oral cancer chemotherapeutics confer cytotoxicity largely by inducing DNA damage, underscoring the importance of the cellular DNA damage repair and response pathways in cancer therapy. However, tumor recurrence and acquired resistance, following the initial response to treatment, remains as a major clinical challenge. By analyzing oral tumor cells derived from the primary and recurrent tumors of the same patient, our study revealed upregulated PARP1 expression in the recurrent tumor cells. Cisplatin and 5-fluorouracil treatment further augmented PARP1 expression in the recurrent, but not the primary, tumor cells. Post-treatment upregulation of PARP1 was dependent on the catalytic activities of PARP and CDK7. Consistent with the established function of PARP1 in DNA repair, we showed that overexpression of PARP1 rendered the primary tumor cells highly resistant to DNA damage treatment. Conversely, PARP inhibition partially reversed the treatment resistance in the recurrent tumor cells; combinatorial treatment using a PARP inhibitor and cisplatin/5-fluorouracil significantly sensitized the tumor response in vivo. Taken together, we reported here PARP1 upregulation as a clinically relevant mechanism involved in oral cancer recurrence, and suggested the clinical benefit of PARP inhibitors, currently approved for the treatment of several other types of cancer, in oral cancer. Frontiers Media S.A. 2022-01-05 /pmc/articles/PMC8769238/ /pubmed/35071239 http://dx.doi.org/10.3389/fcell.2021.804962 Text en Copyright © 2022 Wang, Gouttia, Wang and Peng. https://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 Cell and Developmental Biology
Wang, Feifei
Gouttia, Odjo G.
Wang, Ling
Peng, Aimin
PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance
title PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance
title_full PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance
title_fullStr PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance
title_full_unstemmed PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance
title_short PARP1 Upregulation in Recurrent Oral Cancer and Treatment Resistance
title_sort parp1 upregulation in recurrent oral cancer and treatment resistance
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769238/
https://www.ncbi.nlm.nih.gov/pubmed/35071239
http://dx.doi.org/10.3389/fcell.2021.804962
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