PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting
Poly(ADP-ribose) polymerases have shown true promise in early clinical studies due to reported activity in BRCA-associated cancers. PARP inhibitors may represent a potentially important new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. In order to w...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Termedia Publishing House
2017-02-01
|
| Series: | Menopause Review |
| Subjects: | |
| Online Access: | https://www.termedia.pl/PARP-inhibitors-review-of-mechanisms-of-action-and-BRCA1-2-mutation-targeting,4,29355,1,1.html |
| _version_ | 1831524066075344896 |
|---|---|
| author | Karolina N. Dziadkowiec Emilia Gąsiorowska Ewa Nowak-Markwitz Anna Jankowska |
| author_facet | Karolina N. Dziadkowiec Emilia Gąsiorowska Ewa Nowak-Markwitz Anna Jankowska |
| author_sort | Karolina N. Dziadkowiec |
| collection | DOAJ |
| description | Poly(ADP-ribose) polymerases have shown true promise in early clinical studies due to reported activity in BRCA-associated cancers. PARP inhibitors may represent a potentially important new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. In order to widen the prospective patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. In addition, a more sophisticated understanding of the toxicity profile is required if PARP inhibitors are to be employed in the curative, rather than the palliative, setting. PARP inhibitors have successfully moved into clinical practice in the past few years, with approval granted from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) within the past two years. The United States FDA approval of olaparib applies to fourth-line treatment in germline BRCA-mutant ovarian cancer, and European EMA approval of olaparib for maintenance therapy in both germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. This review covers the current understanding of PARP, its inhibition, and the basis of the excitement surrounding these new agents. It also evaluates future approaches and directions required to achieve full understanding of the intricate interplay of these agents at the cellular level. |
| first_indexed | 2024-12-16T07:26:48Z |
| format | Article |
| id | doaj.art-6e75a2ed5b204fc2aa5f1914b7a5368e |
| institution | Directory Open Access Journal |
| issn | 1643-8876 2299-0038 |
| language | English |
| last_indexed | 2024-12-16T07:26:48Z |
| publishDate | 2017-02-01 |
| publisher | Termedia Publishing House |
| record_format | Article |
| series | Menopause Review |
| spelling | doaj.art-6e75a2ed5b204fc2aa5f1914b7a5368e2022-12-21T22:39:28ZengTermedia Publishing HouseMenopause Review1643-88762299-00382017-02-0115421521910.5114/pm.2016.6566729355PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targetingKarolina N. DziadkowiecEmilia GąsiorowskaEwa Nowak-MarkwitzAnna JankowskaPoly(ADP-ribose) polymerases have shown true promise in early clinical studies due to reported activity in BRCA-associated cancers. PARP inhibitors may represent a potentially important new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. In order to widen the prospective patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. In addition, a more sophisticated understanding of the toxicity profile is required if PARP inhibitors are to be employed in the curative, rather than the palliative, setting. PARP inhibitors have successfully moved into clinical practice in the past few years, with approval granted from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) within the past two years. The United States FDA approval of olaparib applies to fourth-line treatment in germline BRCA-mutant ovarian cancer, and European EMA approval of olaparib for maintenance therapy in both germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. This review covers the current understanding of PARP, its inhibition, and the basis of the excitement surrounding these new agents. It also evaluates future approaches and directions required to achieve full understanding of the intricate interplay of these agents at the cellular level.https://www.termedia.pl/PARP-inhibitors-review-of-mechanisms-of-action-and-BRCA1-2-mutation-targeting,4,29355,1,1.htmlPARP BRCA mutation olaparib ovarian cancer poly(ADP-ribose) polymerases DNA PARP1 PARP2 |
| spellingShingle | Karolina N. Dziadkowiec Emilia Gąsiorowska Ewa Nowak-Markwitz Anna Jankowska PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting Menopause Review PARP BRCA mutation olaparib ovarian cancer poly(ADP-ribose) polymerases DNA PARP1 PARP2 |
| title | PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting |
| title_full | PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting |
| title_fullStr | PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting |
| title_full_unstemmed | PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting |
| title_short | PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting |
| title_sort | parp inhibitors review of mechanisms of action and brca1 2 mutation targeting |
| topic | PARP BRCA mutation olaparib ovarian cancer poly(ADP-ribose) polymerases DNA PARP1 PARP2 |
| url | https://www.termedia.pl/PARP-inhibitors-review-of-mechanisms-of-action-and-BRCA1-2-mutation-targeting,4,29355,1,1.html |
| work_keys_str_mv | AT karolinandziadkowiec parpinhibitorsreviewofmechanismsofactionandbrca12mutationtargeting AT emiliagasiorowska parpinhibitorsreviewofmechanismsofactionandbrca12mutationtargeting AT ewanowakmarkwitz parpinhibitorsreviewofmechanismsofactionandbrca12mutationtargeting AT annajankowska parpinhibitorsreviewofmechanismsofactionandbrca12mutationtargeting |