PARP Inhibitors in BRCA Gene-Mutated Ovarian Cancer and Beyond

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

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Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy

International Journal of Molecular Sciences ◽

10.3390/ijms22084203 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4203

Author(s):

Giorgio Valabrega ◽

Giulia Scotto ◽

Valentina Tuninetti ◽

Arianna Pani ◽

Francesco Scaglione

Keyword(s):

Ovarian Cancer ◽

Signal Transduction ◽

Dna Damage ◽

Chemical Structure ◽

Parp Inhibitors ◽

Mechanisms Of Action ◽

Point Of View ◽

Safety And Efficacy ◽

Damage Repair ◽

Pharmacokinetic Properties

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.

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Out-of-pocket costs for PARP inhibitors high in US Medicare beneficiaries with ovarian cancer

PharmacoEconomics & Outcomes News ◽

10.1007/s40274-021-7423-7 ◽

2021 ◽

Vol 870 (1) ◽

pp. 20-20

Keyword(s):

Ovarian Cancer ◽

Parp Inhibitors ◽

Medicare Beneficiaries ◽

Out Of Pocket Costs

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416 Elucidating resistance mechanism to parp inhibitors for the development of novel therapeutic approaches in high-grade serous ovarian cancer

10.1136/ijgc-2020-esgo.133 ◽

2020 ◽

Author(s):

Hagen Kulbe ◽

Wanja Kassuhn ◽

Frauke Ringel ◽

Gabriele Welsch ◽

Peggy Treffkorn ◽

...

Keyword(s):

Ovarian Cancer ◽

Resistance Mechanism ◽

Parp Inhibitors ◽

High Grade ◽

Serous Ovarian Cancer ◽

Therapeutic Approaches ◽

Novel Therapeutic

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Effects of PARP inhibitors therapy on the PFS and OS in platinum-sensitive recurrent ovarian cancer: A meta-analysis of randomized controlled trials

Gynecologic Oncology ◽

10.1016/j.ygyno.2019.04.630 ◽

2019 ◽

Vol 154 ◽

pp. 271

Author(s):

B.H. Min ◽

S.H. Yoon ◽

S.H. Shim

Keyword(s):

Ovarian Cancer ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Recurrent Ovarian Cancer ◽

Parp Inhibitors ◽

Controlled Trials ◽

Randomized Controlled ◽

Platinum Sensitive

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A MOLECULAR-BASED APPROACH TO INVESTIGATE BREAST CANCER 1 AND BREAST CANCER 2 STATUS IN OVARIAN CANCER AMONG IRAQI WOMEN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i7.25217 ◽

2018 ◽

Vol 11 (7) ◽

pp. 199

Author(s):

Muhannad Shweash ◽

Saddam Jumaa Naseer ◽

Maisam Khider Al-anii ◽

Thulfiqar Fawwaz Mutar

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Gene Mutations ◽

Healthy Controls ◽

Brca1 And Brca2 ◽

First Degree Relatives ◽

Brca Gene ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

Objective: Cancer ovary is one of the fatal gynecologic malignancies worldwide. Since breast cancer (BRCA) genes are considered tumor suppressor genes and play important roles in cancer by repairing of chromosomal damage with the error repair of DNA breaks. Therefore, breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations strongly enhance the development of ovarian cancer risk among women. Here, we report that both genes are an essential mediator of progress ovarian cancer, to determine the influence of BRCA1 and BRCA2 mutations in the improvement of ovarian cancer.Methods: A total of 25 subjects were chosen for the genetic studies, and three groups were recruited: fifteen ovarian cancer patients group, five healthy controls, and five first-degree relatives to a known case of ovarian cancer patients.Results: A genetic analysis revealed that a strong correlation exists between both gene mutations’ status in ovarian cancer, and BRCA gene mutations (185delAG, 5382insC, and 4153delA in BRCA1 and 6174delT in BRCA2) remained to establish to have a relatively high frequency among people in this study among ovarian cancer patients. Furthermore, seven patients with ovarian cancer carried all of the four investigated mutations, and five had three mutations.Conclusion: Otherwise, BRCA gene frequency showed low prevalence among first-degree relatives, and to a lesser extent among healthy controls, with only a few had all of the mutations combined. These data demonstrate for the first time a molecular link between BRCA1 and BRCA2 mutations in ovarian cancer progression in Iraq.

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