scholarly journals MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers

2021 ◽  
Vol 14 (2) ◽  
pp. 100987
Author(s):  
Yue Sun ◽  
Jing Wu ◽  
Xiaoying Dong ◽  
Jingzi Zhang ◽  
Chao Meng ◽  
...  
Keyword(s):  
Parp Inhibitors ◽  
Ovarian Cancers

scholarly journals PARP inhibitors for all ovarian cancers

2019 ◽  
Vol 25 (11) ◽  
pp. 1647-1647 ◽  
Author(s):  
Javier Carmona
Keyword(s):  
Parp Inhibitors ◽  
Ovarian Cancers

scholarly journals Fallopian Tube Carcinoma

2019 ◽  
Vol 15 (7) ◽  
pp. 375-382 ◽  
Author(s):  
Marina Stasenko ◽  
Olga Fillipova ◽  
William P. Tew
Keyword(s):  
Fallopian Tube ◽  
Patient Survival ◽  
Gene Mutations ◽  
Adenosine Diphosphate ◽  
Parp Inhibitors ◽  
Fallopian Tube Carcinoma ◽  
Ovarian Cancers ◽  
Primary Fallopian Tube Carcinoma ◽  
Platinum Based Chemotherapy ◽  
Dose Dense

Primary fallopian tube carcinoma is a rare and difficult to cure disease. It is often grouped under the epithelial ovarian cancer umbrella, together with primary ovarian and peritoneal carcinomas. More recent evidence has suggested that epithelial ovarian cancers originate from a fallopian tube precursor. The mainstay of treatment is surgical cytoreduction and platinum-based chemotherapy. There is much debate over the best timing for surgery and the best approach to delivering the chemotherapy: traditional intravenous once every 3 weeks regimen, versus intraperitoneal, versus dose-dense intravenous regimens. Although these debates continue, novel targeted therapies, including bevacizumab and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors, have emerged. PARP inhibitors are particularly efficacious in patients with BRCA1/2 gene mutations, and their use has been shown to prolong patient survival. This article reviews the pathologic etiology; describes the heredity, treatment challenges, and controversies; and summarizes novel therapies in primary fallopian tube carcinoma.

scholarly journals Beyond Breast and Ovarian Cancers: PARP Inhibitors for BRCA Mutation-Associated and BRCA-Like Solid Tumors

2014 ◽  
Vol 4 ◽  
Author(s):  
Ciara C. O’Sullivan ◽  
Dominic H. Moon ◽  
Elise C. Kohn ◽  
Jung-Min Lee
Keyword(s):  
Solid Tumors ◽  
Brca Mutation ◽  
Parp Inhibitors ◽  
Ovarian Cancers

scholarly journals Ovarian tumor: a review

2021 ◽  
Vol 10 (9) ◽  
pp. 3657
Author(s):  
Poonam Kashyap
Keyword(s):  
Ovarian Cancer ◽  
Brca2 Mutation ◽  
Screening Method ◽  
Progression Free Survival ◽  
Angiogenesis Inhibitors ◽  
Parp Inhibitors ◽  
Brca1 And Brca2 ◽  
Elderly Age ◽  
Ovarian Cancers ◽  
History Of

Ovarian cancers are the 7th most common cancers in women. It is found more commonly in elderly age group. The survival depends on the stage of diagnosis and many of the patients present in advanced disease when the prognosis becomes dismal. The dilemma is to differentiate them from benign disease so that the unwanted laparotomies could be saved. Biomarkers and radiological classification may play a role in differentiating benign from malignant and deciding on the management. There is no screening method to diagnose ovarian cancers and the patient presents with nonspecific complaints missing them in early stages. Optimal cytoreduction is required for better overall survival, progression free survival and response to adjuvant chemotherapy. Those women having history of breast, ovary, endometrial, colorectal cancers should be screened for malignancies and genetic testing is advised. Surgery is the mainstay of treatment followed by chemotherapy. Risk reducing salpingoophorectomy can be offered to women having BRCA1 and BRCA2 mutation carriers after they complete their family. The area of target therapies is the most recent and promising in treatment of ovarian cancer. They are coming in forefront when chemotherapy toxicity, drug resistance are big hurdles in treatment of ovarian cancer. With recent advances and understanding of the biology of ovarian cancer have led to clinical trials of targeted agents. The  angiogenesis inhibitors and polyadenosine diphosphate-ribose polymerase (PARP) inhibitors are the most developed.

Abstract 3212: ONC201 shows efficacy in BRCA-deficient cancer cells and synergy with PARP inhibitors in glioblastoma, breast, prostate, and ovarian cancers

2017 ◽  
Author(s):  
Marie D. Baumeister ◽  
Ozan C. Küçükkase ◽  
Varun V. Prabhu ◽  
David T. Dicker ◽  
Josh E. Allen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Parp Inhibitors ◽  
Ovarian Cancers

scholarly journals Poly (ADP-Ribose) Polymerase Inhibitors: Recent Advances and Future Development

2015 ◽  
Vol 33 (12) ◽  
pp. 1397-1406 ◽  
Author(s):  
Clare L. Scott ◽  
Elizabeth M. Swisher ◽  
Scott H. Kaufmann
Keyword(s):  
Parp Inhibitor ◽  
Germline Mutations ◽  
Parp Inhibitors ◽  
Clinical Development ◽  
Preclinical Studies ◽  
High Grade ◽  
Platinum Sensitive ◽  
Ovarian Cancers ◽  
Recent Advances ◽  
Tumor Types

Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising activity in epithelial ovarian cancers, especially relapsed platinum-sensitive high-grade serous disease. Consistent with preclinical studies, ovarian cancers and a number of other solid tumor types occurring in patients with deleterious germline mutations in BRCA1 or BRCA2 seem to be particularly sensitive. However, it is also becoming clear that germline BRCA1/2 mutations are neither necessary nor sufficient for patients to derive benefit from PARP inhibitors. We provide an update on PARP inhibitor clinical development, describe recent advances in our understanding of PARP inhibitor mechanism of action, and discuss current issues in the development of these agents.

scholarly journals Clinical Implications of DNA Repair Defects in High-Grade Serous Ovarian Carcinomas

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1315 ◽  
Author(s):  
Michela Camilla Milanesio ◽  
Silvia Giordano ◽  
Giorgio Valabrega
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Parp Inhibitors ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Ovarian Cancers ◽  
Mutational Status

Despite significant improvements in surgical and medical management, high grade serous ovarian cancer (HGSOC) still represents the deadliest gynecologic malignancy and the fifth most frequent cause of cancer-related mortality in women in the USA. Since DNA repair alterations are regarded as the “the Achille’s heel” of HGSOC, both DNA homologous recombination and DNA mismatch repair deficiencies have been explored and targeted in epithelial ovarian cancers in the latest years. In this review, we aim at focusing on the therapeutic issues deriving from a faulty DNA repair machinery in epithelial ovarian cancers, starting from existing and well-established treatments and investigating new therapeutic approaches which could possibly improve ovarian cancer patients’ survival outcomes in the near future. In particular, we concentrate on the role of both Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPis) and immune checkpoint inhibitors in HGSOC, highlighting their activity in relation to BRCA1/2 mutational status and homologous recombination deficiency (HRD). We investigate the biological rationale supporting their use in the clinical setting, pointing at tracking their route from the laboratory bench to the patient’s bedside. Finally, we deal with the onset of mechanisms of primary and acquired resistance to PARPis, reporting the pioneering strategies aimed at converting homologous-recombination (HR) proficient tumors into homologous recombination (HR)-deficient HGSOC.

HSR19-091: Incidence of Adverse Events Following Use of Different PARP Inhibitors: Systematic Review and Meta-Analysis

2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-091
Author(s):  
Thanh Ho ◽  
Irbaz Bin Riaz ◽  
Maheen Akhter ◽  
Saad Ullah Malik ◽  
Anum Riaz ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Meta Analysis ◽  
Single Agent ◽  
Parp Inhibitors ◽  
Main Function ◽  
Phase 3 ◽  
Ovid Medline ◽  
Ovarian Cancers ◽  
Number Of Patients ◽  
Grade 3

Background: Poly (ADP-ribose) polymerases (PARPs) are a highly conserved family of enzymes whose main function is to preserve genomic integrity following DNA damage. PARP inhibitors (PARPi) are increasingly used in cancers with deficiencies in homologous recombination. Clinical trials in breast and ovarian cancers have led to several FDA approvals in recent years, and their use in clinical practice is continuing to rise. It is thus necessary to assess their adverse event (AE) profile. Method: Literature search was performed using Ovid MEDLINE, EMBASE, CENTRAL, and Scopus (inception through October 26, 2018). Eligible studies were phase 3, randomized, controlled trials that compared single agent PARPi to placebo or standard treatment. Number of patients treated and AEs reported were recorded. Observed incidence of AE was reported with 95% CI. Heterogeneity was evaluated using Cochran Q statistic and I2 statistics quantified the proportion of heterogeneity not due to chance. Results: Databases revealed 869 references. Of these, 6 were eligible: 2 in breast cancer (OlympiAD, EMBRACA) and 4 in ovarian cancer (NOVA, ARIEL3, SOLO1, SOLO2). PARPi included niraparib (NOVA), olaparib (OlympiAD, SOLO1, SOLO2), rucaparib (ARIEL3), and talazoparib (EMBRACA). Of 1,685 patients who received PARPi, incidence of any AE, regardless of grade, was 98.5% (95% CI, 97.2–99.2%). Common AEs were: nausea (incidence rate, 68.9% and 95% CI, 58.7%–77.5%), fatigue (56.3%, 45.3%–66.8%), anemia (46.3%, 37.2%–55.8%), vomiting (33.7%, 29.5%–38.3%), neutropenia (24.7%, 15.3%–37.4%), headache (23.9%, 19.9%–28.4%), and reduced appetite (21.7%, 19.3%–24.3%). Myeloid neoplasms were rare (1.2%, 0.7%–1.9%). Incidence of grade 3 or higher AE was 44.3% (30.2%–59.5%) and often related to myelosuppression, specifically anemia (24.7%, 15.3%–37.4%), neutropenia (10.7%, 6.6%–16.9%), and thrombocytopenia (5.0%, 1.7%–14.0%). Incidence of serious AE was 24.3% (19.4%–29.9%); dose interruption occurred in 53.3% (41.2%–65.0%) and dose reduction occurred in 39.2% (23.6%–57.4%). 10% (7.4%–13.6%) of patients discontinued therapy due to AE. Death due to AE was rare; less than 1% (0.4%, 0.2%–0.8%) in all trials. Conclusion: Myelosuppression and gastrointestinal toxicities were the most commonly reported AE in 6 randomized phase 3 trials of PARPi for breast and ovarian cancers. Therapy was rarely discontinued due to AE. It remains to be seen whether these results will be reflected in clinical practice.

scholarly journals Clinicopathological Features of Homologous Recombination–Deficient Epithelial Ovarian Cancers: Sensitivity to PARP Inhibitors, Platinum, and Survival

2012 ◽  
Vol 72 (22) ◽  
pp. 5675-5682 ◽  
Author(s):  
Asima Mukhopadhyay ◽  
Elizabeth R. Plummer ◽  
Ahmed Elattar ◽  
San Soohoo ◽  
Bisha Uzir ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Parp Inhibitors ◽  
Clinicopathological Features ◽  
Ovarian Cancers
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