Rucaparib in ovarian cancer: extending the use of PARP inhibitors in the recurrent disease.

Future Oncol

Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Published: December 2018

Rucaparib is a potent inhibitor of poly (ADP-ribose) polymerase (PARP) PARP1, PARP2 and PARP3, and to a lesser extent, PARP4, PARP10, PARP12, PARP15 and PARP16. Study 10 and ARIEL2 evaluated the use of rucaparib as treatment in patients with recurrent high-grade ovarian carcinoma and resulting in approval of rucaparib for patients with both germline and somatic BRCA mutation. Data from the Phase III trial ARIEL3 led to approval in platinum-sensitive disease as maintenance. This article reviews the efficacy, safety, pharmacokinetics and pharmacodynamics of rucaparib as well as future and ongoing trials.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331693PMC
http://dx.doi.org/10.2217/fon-2018-0215DOI Listing

Publication Analysis

Top Keywords

rucaparib
5
rucaparib ovarian
4
ovarian cancer
4
cancer extending
4
extending parp
4
parp inhibitors
4
inhibitors recurrent
4
recurrent disease
4
disease rucaparib
4
rucaparib potent
4

Similar Publications

Some patients with metastatic castration-resistant prostate cancer (mCRPC) possess germline or acquired defects in the DNA damage repair (DDR) genes BRCA1 and BRCA2. Tumors with BRCA mutations exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi) such as olaparib and rucaparib. As a result, molecular diagnostic testing to identify patients with BRCA mutations eligible for the PARPi therapy has become an integral component of managing patients with mCRPC.

View Article and Find Full Text PDF

Background/objectives: Through phase III clinical trials, PARP inhibitors have demonstrated outcome improvements in mCRPC patients with alterations in BRCA1/2 genes who have progressed on a second-generation androgen receptor pathway inhibitor (ARPI). While improving outcomes, PARP inhibitors contribute to the ever-growing economic burden of PCa. The objective of this project is to evaluate the cost-effectiveness of PARP inhibitors (olaparib, rucaparib, or talazoparib) versus the SOC (docetaxel or androgen receptor pathway inhibitors (ARPI)) for previously progressed mCRPC patients with BRCA1/2 mutations from the Canadian healthcare system perspective.

View Article and Find Full Text PDF

and Beyond: Impact on Therapeutic Choices Across Cancer.

Cancers (Basel)

December 2024

Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Blvd, Singapore 168583, Singapore.

Background: Identifying patients with gm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management. This review examines the evidence for the latest predictive and therapeutic approaches in -associated cancers.

Clinical Description: Data supports the use of adjuvant olaparib in patients with gm high-risk HER2-negative breast cancer.

View Article and Find Full Text PDF

A pan-tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors.

CA Cancer J Clin

January 2025

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications.

View Article and Find Full Text PDF

Among the Poly(ADP-ribose) Polymerase (PARP) family in mammals, PARP1 is the first identified and well-studied member that plays a critical role in DNA damage repair and has been proven to be an effective target for cancer therapy. Here, we have reviewed not only the role of PARP1 in different DNA damage repair pathways, but also the working mechanisms of several PARP inhibitors (PARPi), inhibiting Poly-ADP-ribosylation (PARylation) processing and PAR chains production to trap PARP1 on impaired DNA and inducing Transcription- replication Conflicts (TRCs) by inhibiting the PARP1 activity. This review has systematically summarized the latest clinical application of six authorized PARPi, including olaparib, rucaparib, niraparib, talazoparib, fuzuloparib and pamiparib, in monotherapy and combination therapies with chemotherapy, radiotherapy, and immunotherapy, in different kinds of cancer.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!