The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review
Poly(ADP-ribose) polymerase (PARP) inhibitors represent one of the successful novel approaches to targeted cancer treatment. Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these a...
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| Veröffentlicht in: | Cell & bioscience 2020-03, Vol.10 (1), p.35-35, Article 35 |
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| creator | Patel, Mausam Nowsheen, Somaira Maraboyina, Sanjay Xia, Fen |
| description | Poly(ADP-ribose) polymerase (PARP) inhibitors represent one of the successful novel approaches to targeted cancer treatment. Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these agents, certain challenges remain with their use. Among the most important are primary and secondary resistance. Here, we review the mechanism of action of PARP inhibitors and their ability to exploit certain inherent deficiencies among malignant cells to improve cell killing, with a focus on deficiencies in homologous recombination among cells with BRCA1 and BRCA2 mutations. Moreover, we discuss the different mechanisms of resistance including development of secondary resistance and strategies to overcome them. Finally, we discuss the limitations of novel therapeutic interventions and possible future studies to exploit biochemical pathways in order to improve therapeutic efficacy of PARP inhibitors. |
| doi_str_mv | 10.1186/s13578-020-00390-7 |
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Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these agents, certain challenges remain with their use. Among the most important are primary and secondary resistance. Here, we review the mechanism of action of PARP inhibitors and their ability to exploit certain inherent deficiencies among malignant cells to improve cell killing, with a focus on deficiencies in homologous recombination among cells with BRCA1 and BRCA2 mutations. Moreover, we discuss the different mechanisms of resistance including development of secondary resistance and strategies to overcome them. Finally, we discuss the limitations of novel therapeutic interventions and possible future studies to exploit biochemical pathways in order to improve therapeutic efficacy of PARP inhibitors.</description><identifier>ISSN: 2045-3701</identifier><identifier>EISSN: 2045-3701</identifier><identifier>DOI: 10.1186/s13578-020-00390-7</identifier><identifier>PMID: 32180937</identifier><language>eng</language><publisher>LONDON: Springer Nature</publisher><subject>Analysis ; Apoptosis ; Binding sites ; Biochemistry & Molecular Biology ; Biotechnology ; BRCA mutations ; Breast cancer ; Cancer ; Cancer therapies ; Cancer treatment ; Care and treatment ; Clinical trials ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA repair ; Drug approval ; Enzymes ; FDA approval ; Future predictions ; Gene mutation ; Inhibitors ; Life Sciences & Biomedicine ; Metastasis ; Monosaccharides ; Mutation ; Niraparib ; Olaparib ; Ovarian cancer ; PARP ; Poly(ADP-ribose) ; Poly(ADP-ribose) polymerase ; Proteins ; Resistance ; Review ; Ribose ; Rucaparib ; Science & Technology ; Signal transduction ; Talazoparib ; Tumors</subject><ispartof>Cell & bioscience, 2020-03, Vol.10 (1), p.35-35, Article 35</ispartof><rights>The Author(s) 2020.</rights><rights>COPYRIGHT 2020 BioMed Central Ltd.</rights><rights>2020. 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Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these agents, certain challenges remain with their use. Among the most important are primary and secondary resistance. Here, we review the mechanism of action of PARP inhibitors and their ability to exploit certain inherent deficiencies among malignant cells to improve cell killing, with a focus on deficiencies in homologous recombination among cells with BRCA1 and BRCA2 mutations. Moreover, we discuss the different mechanisms of resistance including development of secondary resistance and strategies to overcome them. Finally, we discuss the limitations of novel therapeutic interventions and possible future studies to exploit biochemical pathways in order to improve therapeutic efficacy of PARP inhibitors.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>Binding sites</subject><subject>Biochemistry & Molecular Biology</subject><subject>Biotechnology</subject><subject>BRCA mutations</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cancer treatment</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA repair</subject><subject>Drug approval</subject><subject>Enzymes</subject><subject>FDA approval</subject><subject>Future predictions</subject><subject>Gene mutation</subject><subject>Inhibitors</subject><subject>Life Sciences & Biomedicine</subject><subject>Metastasis</subject><subject>Monosaccharides</subject><subject>Mutation</subject><subject>Niraparib</subject><subject>Olaparib</subject><subject>Ovarian cancer</subject><subject>PARP</subject><subject>Poly(ADP-ribose)</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Proteins</subject><subject>Resistance</subject><subject>Review</subject><subject>Ribose</subject><subject>Rucaparib</subject><subject>Science & Technology</subject><subject>Signal transduction</subject><subject>Talazoparib</subject><subject>Tumors</subject><issn>2045-3701</issn><issn>2045-3701</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYlPZH-ACReJmE8rwRxLHXCBV5avSJBCMa8uxj1tXSdzZTsf49bjtKCvigvgi9vHzvtY5erPsOUaXGDf164BpxZoCEVQgRDkq2KPslKCyKihD-PGD_Ul2FsIKpa_kGLHqaXZCCW4Qp-w0-3m9hNy7DnJn8rXr7s6n774U3rYuwMWu0IOXAXI7LG1ro_MhbfOYVNGDjD0McStVclDgcznovIe4dDrk0eVuA165Pr0AwYa4Zd7kMp02Fm6fZU-M7AKc3f8n2fcP769nn4qrzx_ns-lVoeqaxqKSDWprbRokMaMaGy61rlqOJVQIc82YRBRjyjFlmJSmIsQo3ZgSK0MZaegkm-99tZMrsfa2l_5OOGnFruD8QkgfrepASNWi0nCGFaCScNpULam1bhvJMAdZJq-3e6_12PagVerey-7I9PhmsEuxcBvBUF1RypPB-b2BdzcjhCh6GxR0nRzAjUEQyhjntEwNTbKXf6ErN_ohjWpLcVQTTKo_1EKmBuxgXHpXbU3FtMYMM57ikqjLf1BpaeitcgMYm-pHgosjQWIi_IgLOYYg5t--HrNkzyrvQvBgDvPASGzDKvZhFSmsYhdWwZLoxcNJHiS_o5mAZg_cQutMUBZSeg5YSnOFeYMQ3wYbz2yU0bph5sYhJumr_5fSXxCUA04</recordid><startdate>20200311</startdate><enddate>20200311</enddate><creator>Patel, Mausam</creator><creator>Nowsheen, Somaira</creator><creator>Maraboyina, Sanjay</creator><creator>Xia, Fen</creator><general>Springer Nature</general><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20200311</creationdate><title>The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review</title><author>Patel, Mausam ; 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| subjects | Analysis Apoptosis Binding sites Biochemistry & Molecular Biology Biotechnology BRCA mutations Breast cancer Cancer Cancer therapies Cancer treatment Care and treatment Clinical trials Deoxyribonucleic acid DNA DNA methylation DNA repair Drug approval Enzymes FDA approval Future predictions Gene mutation Inhibitors Life Sciences & Biomedicine Metastasis Monosaccharides Mutation Niraparib Olaparib Ovarian cancer PARP Poly(ADP-ribose) Poly(ADP-ribose) polymerase Proteins Resistance Review Ribose Rucaparib Science & Technology Signal transduction Talazoparib Tumors |
| title | The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review |
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