Abstract
The standard of treatment for advanced ovarian cancer is represented by optimal surgical debulking preceded or followed by chemotherapeutic regimens including taxanes and platinum agents, possibly associated with bevacizumab and/or intraperitoneal therapy. Despite this comprehensive treatment strategy, almost 75% of patients relapse or progress and are therefore candidates for a second-line treatment, showing, at this point, less chemo-sensitivity and worse prognosis. An interesting approach to improve outcomes of these patients has been developed in the last decade, in BRCA-related ovarian cancer. Mutations in one of the BRCA genes result in impaired homologousrecombination DNA repair, which causes genetic abnormalities that promote carcinogenesis. Interestingly, this defect has been exploited by the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors to provide specific cancer cell cytotoxicity. Particularly, the inhibition of PARP in BRCAmutation carriers leads to the persistence of DNA damage usually repaired by the homologousrecombination system, resulting in cell cycle arrest and thus apoptosis. Despite the mechanism of action, an activity of PARP inhibitors was also observed in “BRCAness” ovarian tumors, and in BRCA-related tumors other than ovarian, suggesting that these agents may be active regardless of BRCA mutation status or site of origin. This review aims to describe the principal evidence that led to the development and the study of PARP inhibitors and to discuss their main implications in our daily clinical practice.
Keywords: Ovarian cancer, BRCA, homologous recombination, PARP inhibitor, DNA repair, apoptosis.
Current Cancer Drug Targets
Title:Parp Inhibitors for the Treatment of Ovarian Cancer
Volume: 18 Issue: 9
Author(s): Laura Cortesi, Angela Toss*Iole Cucinotto
Affiliation:
- Department of Oncology and Haematology, University Hospital of Modena and Reggio Emilia, 41124 Modena,Italy
Keywords: Ovarian cancer, BRCA, homologous recombination, PARP inhibitor, DNA repair, apoptosis.
Abstract: The standard of treatment for advanced ovarian cancer is represented by optimal surgical debulking preceded or followed by chemotherapeutic regimens including taxanes and platinum agents, possibly associated with bevacizumab and/or intraperitoneal therapy. Despite this comprehensive treatment strategy, almost 75% of patients relapse or progress and are therefore candidates for a second-line treatment, showing, at this point, less chemo-sensitivity and worse prognosis. An interesting approach to improve outcomes of these patients has been developed in the last decade, in BRCA-related ovarian cancer. Mutations in one of the BRCA genes result in impaired homologousrecombination DNA repair, which causes genetic abnormalities that promote carcinogenesis. Interestingly, this defect has been exploited by the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors to provide specific cancer cell cytotoxicity. Particularly, the inhibition of PARP in BRCAmutation carriers leads to the persistence of DNA damage usually repaired by the homologousrecombination system, resulting in cell cycle arrest and thus apoptosis. Despite the mechanism of action, an activity of PARP inhibitors was also observed in “BRCAness” ovarian tumors, and in BRCA-related tumors other than ovarian, suggesting that these agents may be active regardless of BRCA mutation status or site of origin. This review aims to describe the principal evidence that led to the development and the study of PARP inhibitors and to discuss their main implications in our daily clinical practice.
Export Options
About this article
Cite this article as:
Cortesi Laura, Toss Angela *, Cucinotto Iole , Parp Inhibitors for the Treatment of Ovarian Cancer, Current Cancer Drug Targets 2018; 18 (9) . https://dx.doi.org/10.2174/1568009618666180308104646
DOI https://dx.doi.org/10.2174/1568009618666180308104646 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Integrins in Drug Targeting-RGD Templates in Toxins
Current Pharmaceutical Design Pharmacogenetics of Estrogen Metabolism and Transport in Relation to Cancer
Current Drug Metabolism Can an Apple a Day Keep the Doctor Away?
Current Pharmaceutical Design Editorial [Hot Topic: Targeted Alpha Therapy – Part II (Guest Editor: Jorgen Elgqvist)]
Current Radiopharmaceuticals Working Towards the Development of Vaccines for the Treatment and Prevention of Early Breast Cancer
Current Cancer Therapy Reviews Human Serum Albumin Conjugated Biomolecules for Cancer Molecular Imaging
Current Pharmaceutical Design Imatinib Mesylate for the Treatment of Solid Tumours: Recent Trials and Future Directions
Current Enzyme Inhibition Mechanisms of Resistance to Photodynamic Therapy
Current Medicinal Chemistry Ribosome Display and Selection of Human Anti-Placental Growth Factor scFv Derived from Ovarian Cancer Patients
Protein & Peptide Letters Synthesis and Antiproliferative Assay of Norcantharidin Derivatives in Cancer Cells
Medicinal Chemistry Human Carbonyl Reductases
Current Drug Metabolism Pharmacological Modulation of Reactive Oxygen Species in Cancer Treatment
Current Drug Targets MicroRNAs in Breast Cancer: One More Turn in Regulation
Current Drug Targets Epigenome-Wide Association Studies (EWAS) in Cancer
Current Genomics Polyisoprenylated Cysteinyl Amide Inhibitors: A Novel Approach to Controlling Cancers with Hyperactive Growth Signaling
Current Medicinal Chemistry Indolinones as Promising Scaffold as Kinase Inhibitors: A Review
Mini-Reviews in Medicinal Chemistry Evaluation of Anticancer, Antibacterial and Antioxidant Properties of a Medicinally Treasured Fern Tectaria coadunata with its Phytoconstituents Analysis by HR-LCMS
Anti-Cancer Agents in Medicinal Chemistry SPARC in Tumor Pathophysiology and as a Potential Therapeutic Target
Current Pharmaceutical Design Bioluminescence Imaging in Rodents: When Light Illuminates Cancer Research
Current Molecular Imaging (Discontinued) Ovarian Granulosa Cell Tumor: A Clinicoradiologic Series with Literature Review
Current Medical Imaging