Novel poly-ADP-ribose polymerase inhibitor combination strategies in ovarian cancer

Purpose of review The recent United States Food and Drug Administration approvals of niraparib and olaparib as maintenance monotherapy for platinum-sensitive, high-grade ovarian cancers independent of BRCA status reflect a willingness to seek indications for poly-ADP-ribose polymerase (PARP) inhibitors beyond cancers with deleterious breast cancer 1 and breast cancer 2 mutations. In this review, I describe the rationale behind current PARP combination clinical trials with chemotherapies, angiogenesis inhibitors, cell cycle checkpoint inhibitors, and inhibitors of the phosphoinositide 3-kinase/AK thymoma/mechanistic target of rapamycin pathway. Recent findings PARP inhibitors have primarily been studied as monotherapy in cancers with homologous recombination repair defects based on an early understanding of PARP-1 as a base excision repair enzyme and the idea that abrogation of two DNA repair pathways cripples rapidly dividing cancer cells. It is now known that PARP-1 is a DNA damage sensor with much wider reaching roles in DNA repair processes and normal cellular functions, opening possibilities for PARP inhibitor use in other clinical contexts. Summary PARP inhibitor combination clinical trials are in the early stages, but will deepen our understanding of DNA repair mechanisms, cancer biology, and targeted therapies, thus contributing to the next iteration of therapeutic options for our patients.
Source: Current Opinion in Obstetrics and Gynecology - Category: OBGYN Tags: GYNECOLOGIC ONCOLOGY: Edited by Gottfried E. Konecny Source Type: research

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AbstractChoosing the optimal therapy for a patient's cancer has long been based on whether the cancer demonstrates a predictive marker of efficacy. The U.S. Food and Drug Administration (FDA) has now approved use of a targeted therapy based solely on tumor molecular markers (pembrolizumab for tumors with deficient mismatch repair [MMR] and high microsatellite instability [MSI]) and approved another therapy based solely on a germline mutation as the predictive marker of benefit (olaparib for BRCA carriers with ovarian or breast cancer) [New Engl J Med 2017;377:1409–1412, N Engl J Med 2012;366:1382–1392, N Eng J ...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Precision Medicine, Breast Cancer Precision Medicine Clinic: Molecular Tumor Board Source Type: research
This study's researchers approached all people turning 85 in 2006 in two cities in the UK for participation. At the beginning of the study in 2006-2007, there were 722 participants, 60 percent of whom were women. The participants provided researchers with information about what they ate every day, their body weight and height measurements, their overall health assessment (including any level of disability), and their medical records. The researchers learned that more than one-quarter (28 percent) of very old adults had protein intakes below the recommended dietary allowance. The researchers noted that older adults w...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Harvey A, Mielke N, Grimstead JW, Jones RE, Nguyen T, Mueller M, Baird DM, Hendrickson EA Abstract Poly-ADP ribose polymerase 1 (PARP1) is clinically important because of its synthetic lethality with breast cancer allele 1 and 2 mutations, which are causative for inherited breast and ovarian cancers. Biochemically, PARP1 is a single-stranded DNA break repair protein that is needed for preserving genomic integrity. In addition, PARP1 has been implicated in a veritable plethora of additional cellular pathways and thus its precise contribution(s) to human biology has remained obscure. To help address this def...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Varol U, Kucukzeybek Y, Alacacioglu A, Somali I, Altun Z, Aktas S, Oktay Tarhan M Abstract BRCA1 and BRCA2 are the genes related with breast and ovarian cancer. They have function in DNA repair processes and thus they are tumor suppressor genes. There are hundreds of mutations identified in these genes. Functional deficiencies due to these mutations impair DNA repair and cause irregularities in the DNA synthesis. The standard method for the laboratory assessment of these BRCA genes includes comprehensive sequencing and testing of broad genomic rearrangements. Members of the families with BRCA mutations hav...
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
Publication date: Available online 14 October 2018Source: Journal of Geriatric OncologyAuthor(s): Gabor Liposits, Kah Poh Loh, Enrique Soto-Perez-de-Celis, Lucy Dumas, Nicolò Matteo Luca Battisti, Sindhuja Kadambi, Capucine Baldini, Susana Banerjee, Stuart M. LichtmanAbstractBreast and ovarian cancer are common malignancies among older adults, causing significant morbidity and mortality. Although most cases of breast and ovarian cancer are sporadic, a significant proportion is caused by mutations in cancer susceptibility genes, most often breast cancer susceptibility genes (BRCA) 1 and 2. Furthermore, some breast an...
Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research
University of Leicester researchers soon will open the first molecularly stratified clinical trial for malignant mesothelioma with the hope of moving the future of treatment toward more personalization. The phase II trial in the United Kingdom is designed to match therapy with a patient’s specific genetic profile. “We’re trying to bring the right drug to the right patient at the right time,” Professor Dean Fennell, chair of thoracic medical oncology at Leicester and chief trial investigator, told Asbestos.com. “We need to find different treatments that work for different people. This is a step...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Mutations in DNA repair pathways, including breast-cancer susceptibility gene 1 (BRCA1) and breast-cancer susceptibility gene 2 (BRCA2) mutation carries, predispose women to an elevated lifetime risk for ovarian cancer (OC) and breast cancer (BC) (National Comprehensive Cancer Network Guidelines, 2018). While the role of bilateral risk-reducing mastectomy is still controversial, risk-reducing salpingo-oophorectomy (RRSO) represents nowadays the main effective prophylactic OC risk measure that should be proposed to BRCA carries, especially once childbearing is complete (National Comprehensive Cancer Network Guidelines, 2018...
Source: Critical Reviews in Oncology Hematology - Category: Cancer & Oncology Authors: Source Type: research
Abstract Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) are the most well‑known genes linked to breast cancer and ovarian cancer, which are crucial in DNA repair and transcriptional regulation. The present study aimed to elucidate the expression profiles, mutations and interaction networks of BRCA1 and BRCA2, which may provide insights to reveal the mechanisms of BRCA genes ultimately leading to breast or ovarian tumorigenesis. Bioinformatics analyses were performed in the present study. The mRNA levels of BRCA1 and BRCA2 were evaluated using FIREHOSE analysis, SAGE Genie tools and Oncomine analys...
Source: International Journal of Molecular Medicine - Category: Molecular Biology Authors: Tags: Int J Mol Med Source Type: research
Cancer is never an easy foe, but some types are more stubborn than others. Ovarian cancer is one of the hardest to treat. But there are signs of progress. Several recent studies have used new combination treatment strategies, including a drug that may make chemotherapy more effective and a drug originally designed to treat breast cancer. More research is needed, but the new studies provide hope for improving outcomes for women with advanced ovarian cancer, when there was little before. On its face, ovarian cancer isn’t actually more difficult to treat than other cancers like breast, prostate or lung. It is, technical...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized Cancer healthytime Innovation Health Source Type: news
Authors: Wang F, Zhu Y, Fang S, Li S, Liu S Abstract Ovarian cancer is the leading cause of mortality resulting from gynecologic cancer. A common anti-ovarian tumor drug is cisplatin; however, repeated use of cisplatin causes severe resistance and leads to poor long-term survival rate in ovarian cancer patients. Recently, it was reported that lanthanum chloride (LaCl3) may inhibit tumor growth and induce apoptosis in certain cancer cells. In the present study, the effect of LaCl3 on ovarian cancer was determined in vivo and in vitro. A cisplatin-sensitive human ovarian cancer cell line, COC1, was used in the curren...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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