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
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...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
-
αvβ3 Integrin-Targeted Peptide/Peptidomimetic-Drug Conjugates: In-Depth Analysis of the Linker Technology
Current Topics in Medicinal Chemistry Intraperitoneal Chemotherapy as Primary Treatment of Advanced Ovarian Cancer:Efficacy, Toxicity, and Future Directions
Reviews on Recent Clinical Trials Pleiotropic Effects of Tocotrienols and Quercetin on Cellular Senescence: Introducing the Perspective of Senolytic Effects of Phytochemicals
Current Drug Targets Cinnamic Acid Derivatives as Anticancer Agents-A Review
Current Medicinal Chemistry A Phase I Study of OMN54 (Aneustat™) in Patients with Advanced Malignancies
Clinical Cancer Drugs Identification of Novel Drug Targets for Angiostatic Cancer Therapy; It Takes Two to Tango
Current Pharmaceutical Design Recognition of Nucleic Acids by Toll-Like Receptors and Development of Immunomodulatory Drugs
Current Medicinal Chemistry Acridine Orange is an Effective Anti-Cancer Drug that Affects Mitochondrial Function in Osteosarcoma Cells
Current Pharmaceutical Design Emerging Role of Wnt/Beta-Catenin Signalling Pathways in Cancer Progression and Role of Small Molecule Tankyrase Inhibitors in Combating Multistage Cancers
Current Cancer Therapy Reviews Targeting Hsp90 in Non-Cancerous Maladies
Current Topics in Medicinal Chemistry Neurotoxicity Associated with Platinum-Based Anti-Cancer Agents: What are the Implications of Copper Transporters?
Current Medicinal Chemistry NOB1: A Potential Biomarker or Target in Cancer
Current Drug Targets Trans-Platinum Complexes in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets
Current Cancer Drug Targets Receptor Tyrosine Kinases: The Main Targets for New Anticancer Therapy
Current Drug Targets Estrogen(s) and Analogs as a Non-Immunogenic Endogenous Ligand in Targeted Drug/DNA Delivery
Current Medicinal Chemistry Synthesis of Phenol-derivatives and Biological Screening for Anticancer Activity
Anti-Cancer Agents in Medicinal Chemistry Tools For Decision-Making In Older Cancer Patients. Role Of The Comprehensive Geriatric Assessment
Anti-Cancer Agents in Medicinal Chemistry Immunomodulation and Anti-inflammatory Roles of Polyphenols as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry HIV-1 Vpr: Enhancing Sensitivity of Tumors to Apoptosis
Current Drug Delivery