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Parp inhibitor ovarian ca

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https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#1
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29132681/-dna-repair-as-a-therapeutic-target
#2
REVIEW
Lauriane Eberst, Medhi Brahmi, Philippe A Cassier
The transmission of an intact and stable genetic code at each cell division relies on different DNA repair systems. Germline mutations of some of these genes cause cancer predisposition, whereas somatic mutations are frequently found in various cancer types, generating genomic instability. As a consequence, cancer cell becomes more susceptible to additional DNA damage. Pharmacological inhibition of DNA repair pathways exploits this frailty: it triggers more damages than cancer cell can tolerate, finally leading to apoptosis...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29117515/metformin-and-epothilone-a-treatment-up-regulate-pro-apoptotic-parp-1-casp-3-and-h2ax-genes-and-decrease-of-akt-kinase-level-to-control-cell-death-of-human-hepatocellular-carcinoma-and-ovary-adenocarcinoma-cells
#3
Aneta Rogalska, Barbara Bukowska, Agnieszka Marczak
High mortality rates in ovarian and liver cancer are largely a result of resistance to currently used chemotherapy. Here, we investigated genotoxic and pro-oxidant effects of metformin (MET) and epothilone A (A) in combination with respect to apoptosis in HepG2 and SKOV-3 cancer cells. Reactive oxygen species (ROS) was studied using 2',7'-dichlorodihydrofluoresein diacetate, and samples were analyzed for the presence and absence of the N-acetylcysteine (NAC). Expression of genes involved in programmed cell death, oxidative and alkylating DNA damage was measured...
November 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29109859/candidate-synthetic-lethality-partners-to-parp-inhibitors-in-the-treatment-of-ovarian-clear-cell-cancer
#4
Naoki Kawahara, Kenji Ogawa, Mika Nagayasu, Mai Kimura, Yoshikazu Sasaki, Hiroshi Kobayashi
Inhibitors of poly(ADP-ribose) polymerase (PARP) are new types of personalized treatment of relapsed platinum-sensitive ovarian cancer harboring BRCA1/2 mutations. Ovarian clear cell cancer (CCC), a subset of ovarian cancer, often appears as low-stage disease with a higher incidence among Japanese. Advanced CCC is highly aggressive with poor patient outcome. The aim of the present study was to determine the potential synthetic lethality gene pairs for PARP inhibitions in patients with CCC through virtual and biological screenings as well as clinical studies...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29081841/niraparib-in-ovarian-cancer-results-to-date-and-clinical-potential
#5
REVIEW
Davide Caruso, Anselmo Papa, Silverio Tomao, Patrizia Vici, Pierluigi Benedetti Panici, Federica Tomao
Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy...
September 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29063517/parp-inhibitors-in-the-treatment-of-triple-negative-breast-cancer
#6
REVIEW
Jill J J Geenen, Sabine C Linn, Jos H Beijnen, Jan H M Schellens
Breast cancer is a heterogeneous disease, manifesting in a broad differentiation in phenotypes and morphologic profiles, resulting in variable clinical behavior. Between 10 and 20% of all breast cancers are triple negative. Triple-negative breast cancer (TNBC) lacks the expression of human epidermal growth factor receptor 2 (HER2) and hormone receptors; therefore, to date, chemotherapy remains the backbone of treatment. TNBC tends to be aggressive and has a high histological grade, resulting in a poor 5-year prognosis...
October 23, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29050241/combination-treatment-with-rucaparib-rubraca-and-mdm2-inhibitors-nutlin-3-and-rg7388-has-synergistic-and-dose-reduction-potential-in-ovarian-cancer
#7
Maryam Zanjirband, Nicola Curtin, Richard J Edmondson, John Lunec
Ovarian cancer is the seventh most common cancer worldwide for females and the most lethal of all gynecological malignancies. The treatment of ovarian cancer remains a challenge in spite of advances in debulking surgery and changes in both chemotherapy schedules and routes of administration. Cancer treatment has recently been improving with the introduction of targeted therapies to achieve greater specificity and less cytotoxicity. Both PARP inhibitors and MDM2-p53 binding antagonists are targeted therapeutic agents entered into clinical trials...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29040190/novel-therapeutics-for-ovarian-cancer-the-11th-biennial-rivkin-center-ovarian-cancer-research-symposium
#8
Neil Johnson, John B Liao
OBJECTIVE: The aim of this study was to summarize developments in novel therapeutics for ovarian cancer presented at the Ovarian Cancer Research Symposium held at the University of Washington. METHODS: A symposium of the leaders in ovarian cancer research was convened to present and discuss current advances and future directions in ovarian cancer research. RESULTS: The fourth session was held on September 13, 2016, and focused on Novel Therapeutics for Ovarian Cancer...
October 17, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29037806/parp-inhibitors-clinical-utility-and-possibilities-of-overcoming-resistance
#9
REVIEW
Benjamin G Bitler, Zachary L Watson, Lindsay J Wheeler, Kian Behbakht
PARP inhibitors represent a major breakthrough in ovarian cancer care. Almost half of all ovarian cancers have deficiencies in the homologous recombination (HR) DNA repair pathway, namely BRCA1/2 mutations. Given the limited therapeutic options for recurrent ovarian cancer patients there has been a significant effort to develop novel therapies to exploit DNA repair deficiencies. In 2005 and 2006, inhibiting PARP enzymes was first observed to be highly effective against cancers with HR deficiencies. PARP inhibitors are being utilized in the clinic to manage recurrent ovarian cancers that display defects in the HR repair pathway...
December 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29037805/tolerance-and-toxicity-of-the-parp-inhibitor-olaparib-in-older-women-with-epithelial-ovarian-cancer
#10
Lauren E Dockery, William P Tew, Kai Ding, Kathleen N Moore
OBJECTIVES: The objective of this study was to determine the overall tolerability and toxicity of olaparib capsules among older (≥65years) patients with recurrent ovarian cancer treated on 8 completed prospective trials of olaparib. METHODS: An ancillary data analysis of 398 patients with recurrent ovarian cancer enrolled on eight prospective trials of olaparib capsules was performed. Patients aged 65years and older were stratified into age groups by 5year increments (ages 65-69, 70-74, ≥75years) and compared to those <65...
October 13, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28994564/targeted-therapy-for-ovarian-cancer-the-rapidly-evolving-landscape-of-parp-inhibitor-use
#11
Christine Walsh
INTRODUCTION: PARP (poly(ADP-ribose) polymerase) inhibitors are a targeted therapy option for ovarian cancer. The goal of this review was to organize and summarize the clinical trials evaluating PARP inhibitor therapy in ovarian cancer as monotherapy, maintenance therapy after partial or complete remission to therapy or as a part of a combination regimen. EVIDENCE ACQUISITION: PubMed, ClinicalTrials.gov, data from the United States Food and Drug Administration (US FDA) and proceedings from scientific conferences were searched for published and unpublished data pertaining to clinical trials and approvals of PARP inhibitor use in ovarian cancer...
October 9, 2017: Minerva Ginecologica
https://www.readbyqxmd.com/read/28994419/targeted-therapy-ariel3-broad-benefit-of-parp-inhibitors-in-ovarian-cancer
#12
David Killock
No abstract text is available yet for this article.
December 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28984489/directing-the-use-of-ddr-kinase-inhibitors-in-cancer-treatment
#13
Inger Brandsma, Emmy D G Fleuren, Chris T Williamson, Christopher J Lord
Defects in the DNA damage response (DDR) drive the development of cancer by fostering DNA mutation but also provide cancer-specific vulnerabilities that can be exploited therapeutically. The recent approval of three different PARP inhibitors for the treatment of ovarian cancer provides the impetus for further developing targeted inhibitors of many of the kinases involved in the DDR, including inhibitors of ATR, ATM, CHEK1, CHEK2, DNAPK and WEE1. Areas covered: We summarise the current stage of development of these novel DDR kinase inhibitors, and describe which predictive biomarkers might be exploited to direct their clinical use...
October 14, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28981112/berberine-induces-oxidative-dna-damage-and-impairs-homologous-recombination-repair-in-ovarian-cancer-cells-to-confer-increased-sensitivity-to-parp-inhibition
#14
Dong Hou, Guangwei Xu, Caibo Zhang, Boxuan Li, Junchao Qin, Xiaohe Hao, Qiao Liu, Xiyu Zhang, Jinsong Liu, Jianjun Wei, Yaoqin Gong, Zhaojian Liu, Changshun Shao
Many cancer drugs exert their therapeutic effect by inducing oxidative stress in the cancer cells. Oxidative stress compromises cell survival by inflicting lesions in macromolecules like DNA. Cancer cells rely on enhanced antioxidant metabolism and increased DNA repair function to survive oxidative assault. PARP1, a protein that senses DNA-strand breaks and orchestrates their repair, has an important role in the repair of oxidative DNA damage. Berberine, an alkaloid compound present in many herbal plants, is capable of inducing oxidative DNA damage and downregulating homologous recombination repair (HRR) in cancer cells...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28979099/investigating-isoquinoline-derivatives-for-inhibition-of-inhibitor-of-apoptosis-proteins-for-ovarian-cancer-treatment
#15
Chen Chen, Jie Wu, Pengfei Zhu, Congjian Xu, Liangqing Yao
OBJECTIVE: To discover novel isoquinoline derivatives for inhibition of inhibitor of apoptosis proteins (IAP) for the treatment of ovarian cancer. METHODS: We first synthesized 533 isoquinoline derivatives, and screened them using CCK-8 to measure their antiproliferative activity. These compounds were further tested by Hoechst staining and flow cytometric analysis to assess proapoptotic activity. The in vivo antitumor efficacy and safety of the screened compounds were evaluated on the xenograft mouse model...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28978184/poly-adp-ribose-polymerase-inhibitors-as-radiosensitizers-a-systematic-review-of-pre-clinical-and-clinical-human-studies
#16
REVIEW
Paul Lesueur, François Chevalier, Jean-Baptiste Austry, Waisse Waissi, Hélène Burckel, Georges Noël, Jean-Louis Habrand, Yannick Saintigny, Florence Joly
BACKGROUND: Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974545/the-hrd-decision-which-parp-inhibitor-to-use-for-whom-and-when
#17
Elise C Kohn, Jung-Min Lee, S Percy Ivy
Rucaparib, a polyADPribose polymerase (PARP) inhibitor, was approved recently for use in women with high grade serous ovarian cancer (HGSOC). It is now one of 3 approved PARPi for use in recurrent ovarian cancer, a family of agents that has changed the HGSOC treatment landscape and outcome.
October 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28934130/isoliquiritigenin-induces-autophagy-and-inhibits-ovarian-cancer-cell-growth
#18
Hsin-Yuan Chen, Tsui-Chin Huang, Tzong-Ming Shieh, Chi-Hao Wu, Li-Chun Lin, Shih-Min Hsia
Ovarian cancer is one of the commonest gynecologic malignancies, which has a poor prognosis for patients at the advanced stage. Isoliquiritigenin (ISL), an active flavonoid component of the licorice plant, previously demonstrated antioxidant, anti-inflammatory, and tumor suppressive effects. In this study, we investigated the antitumor effect of ISL on human ovarian cancer in vitro using the human ovarian cancer cell lines, OVCAR5 and ES-2, as model systems. Our results show that ISL significantly inhibited the viability of cancer cells in a concentration- and time-dependent manner...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28933580/the-role-of-cediranib-in-ovarian-cancer
#19
Cecilia Orbegoso, Gloria Marquina, Angela George, Susana Banerjee
Treatment options for relapsed ovarian cancer have increased over the decade with the addition of targeted agents, such as PARP inhibitors and antiangiogenic agents. Bevacizumab, a monoclonal antibody binding vascular endothelial growth factor (VEGF), was the first anti-angiogenic agent to be incorporated in the ovarian cancer treatment landscape. Other molecules utilising different mechanisms of action to target angiogenesis have been developed, including cediranib, an oral potent inhibitor of VEGF Tyrosine Kinase Inhibitor that has demonstrated activity in both phase II and phase III studies...
October 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28925391/ezh2-contributes-to-the-response-to-parp-inhibitors-through-its-parp-mediated-poly-adp-ribosylation-in-breast-cancer
#20
H Yamaguchi, Y Du, K Nakai, M Ding, S-S Chang, J L Hsu, J Yao, Y Wei, L Nie, S Jiao, W-C Chang, C-H Chen, Y Yu, G N Hortobagyi, M-C Hung
Inhibitors against poly (ADP-ribose) polymerase (PARP) are promising targeted agents currently used to treat BRCA-mutant ovarian cancer and are in clinical trials for other cancer types, including BRCA-mutant breast cancer. To enhance the clinical response to PARP inhibitors (PARPis), understanding the mechanisms underlying PARPi sensitivity is urgently needed. Here, we show enhancer of zeste homolog 2 (EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells...
September 18, 2017: Oncogene
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