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Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy

DNA damage repair plays a key role in maintaining genomic stability and integrity. Flap endonuclease 1 (FEN1) is a core protein in the base excision repair (BER) pathway and participates in Okazaki fragment maturation during DNA replication. Several studies have implicated FEN1 in the regulation of...

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Detalles Bibliográficos
Autores principales: Yang, Fan, Hu, Zhigang, Guo, Zhigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312813/
https://www.ncbi.nlm.nih.gov/pubmed/35883563
http://dx.doi.org/10.3390/biom12071007
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author Yang, Fan
Hu, Zhigang
Guo, Zhigang
author_facet Yang, Fan
Hu, Zhigang
Guo, Zhigang
author_sort Yang, Fan
collection PubMed
description DNA damage repair plays a key role in maintaining genomic stability and integrity. Flap endonuclease 1 (FEN1) is a core protein in the base excision repair (BER) pathway and participates in Okazaki fragment maturation during DNA replication. Several studies have implicated FEN1 in the regulation of other DNA repair pathways, including homologous recombination repair (HRR) and non-homologous end joining (NHEJ). Abnormal expression or mutation of FEN1 in cells can cause a series of pathological responses, leading to various diseases, including cancers. Moreover, overexpression of FEN1 contributes to drug resistance in several types of cancers. All this supports the hypothesis that FEN1 could be a therapeutic target for cancer treatment. Targeting FEN1 has been verified as an effective strategy in mono or combined treatment of cancer. Small-molecule compounds targeting FEN1 have also been developed and detected in cancer regression. In this review, we summarize the recent development of small-molecule inhibitors targeting FEN1 in recent years, thereby expanding their therapeutic potential and application.
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spelling pubmed-93128132022-07-26 Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy Yang, Fan Hu, Zhigang Guo, Zhigang Biomolecules Review DNA damage repair plays a key role in maintaining genomic stability and integrity. Flap endonuclease 1 (FEN1) is a core protein in the base excision repair (BER) pathway and participates in Okazaki fragment maturation during DNA replication. Several studies have implicated FEN1 in the regulation of other DNA repair pathways, including homologous recombination repair (HRR) and non-homologous end joining (NHEJ). Abnormal expression or mutation of FEN1 in cells can cause a series of pathological responses, leading to various diseases, including cancers. Moreover, overexpression of FEN1 contributes to drug resistance in several types of cancers. All this supports the hypothesis that FEN1 could be a therapeutic target for cancer treatment. Targeting FEN1 has been verified as an effective strategy in mono or combined treatment of cancer. Small-molecule compounds targeting FEN1 have also been developed and detected in cancer regression. In this review, we summarize the recent development of small-molecule inhibitors targeting FEN1 in recent years, thereby expanding their therapeutic potential and application. MDPI 2022-07-20 /pmc/articles/PMC9312813/ /pubmed/35883563 http://dx.doi.org/10.3390/biom12071007 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Yang, Fan
Hu, Zhigang
Guo, Zhigang
Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy
title Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy
title_full Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy
title_fullStr Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy
title_full_unstemmed Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy
title_short Small-Molecule Inhibitors Targeting FEN1 for Cancer Therapy
title_sort small-molecule inhibitors targeting fen1 for cancer therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312813/
https://www.ncbi.nlm.nih.gov/pubmed/35883563
http://dx.doi.org/10.3390/biom12071007
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