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Parp inhibitor ovarian ca

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https://www.readbyqxmd.com/read/28646535/targeting-stat3-by-ho3867-induces-apoptosis-in-ovarian-clear-cell-carcinoma
#1
Kristin Bixel, Uksha Saini, Hemant Kumar Bid, John Fowler, Maria Riley, Ross Wanner, Kalpana Deepa Priya Dorayappan, Sneha Rajendran, Ikuo Konishi, Noriomi Matsumura, David E Cohn, Karuppaiyah Selvendiran
Advanced ovarian clear cell carcinoma (OCCC) carries a very poor prognosis in large part secondary to the extremely high rate of resistance to standard platinum and taxane chemotherapy. STAT3 expression and activation has been shown to regulate tumor progression in various human cancers, though has not been well studied in OCCC. Preliminary work in our lab has demonstrated constitutive activation of STAT3 (pSTAT3Tyr705 or pSTAT3727) in OCCC cell lines as well as human OCCC tumor tissue samples. Significantly, pSTAT3 is expressed in the absence of other forms of activated STAT (pSTAT1, 2, 6)...
June 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28646019/functionally-null-rad51d-missense-mutation-associates-strongly-with-ovarian-carcinoma
#2
Barbara Rivera, Massimo Di Iorio, Jessica Frankum, Javad Nadaf, Somayyeh Fahiminiya, Suzanna L Arcand, David L Burk, Damien Grapton, Eva Tomiak, Valerie Hastings, Nancy Hamel, Rabea Wagener, Olga Aleynikova, Sylvie Giroux, Fadi F Hamdan, Alexandre Dionne-Laporte, George Zogopoulos, Francois Rousseau, Albert M Berghuis, Diane Provencher, Guy A Rouleau, Jacques L Michaud, Anne-Marie Mes-Masson, Jacek Majewski, Susanne Bens, Reiner Siebert, Steven A Narod, Mohammad R Akbari, Christopher J Lord, Patricia N Tonin, Alexandre Orthwein, William D Foulkes
RAD51D is a key player in DNA repair by homologous recombination (HR) and RAD51D truncating mutation carriers have an increased risk for ovarian cancer (OC). However, the contribution of non-truncating RAD51D variants to cancer predisposition remains uncertain. Using deep sequencing and case-control genotyping studies, we show that in French Canadians, the missense RAD51D variant c.620C>T;p.S207L is highly prevalent and is associated with a high risk for ovarian high-grade serous carcinoma (HGSC) (3.8% cases vs 0...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28643177/targeting-dna-repair-and-replication-stress-in-the-treatment-of-ovarian-cancer
#3
REVIEW
Junko Murai
Approximately half of high-grade serous epithelial ovarian cancers incur alterations in genes of homologous recombination (BRCA1, BRCA2, RAD51C, Fanconi anemia genes), and the rest incur alterations in other DNA repair pathways at high frequencies. Such cancer-specific gene alterations can confer selective sensitivity to DNA damaging agents such as cisplatin and carboplatin, topotecan, etoposide, doxorubicin, and gemcitabine. Originally presumed to inhibit DNA repair, PARP inhibitors that have recently been approved by the FDA for the treatment of advanced ovarian cancer also act as DNA damaging agents by inducing PARP-DNA complexes...
June 22, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#4
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28625311/cancers-de-l%C3%A2-ovaire-brca-mut%C3%A3-consultation-d%C3%A2-oncog%C3%A3-n%C3%A3-tique-et-prescription-des-inhibiteurs-de-parp
#5
Laurence Gladieff, Dominique Stoppa Lyonnet, Alain Lortholary, Alexandra Leary, Catherine Genestie, Isabelle Ray-Coquard
GENETIC COUNSELING AND PARP INHIBITORS PRESCRIPTION: Upon the availability of the PARP inhibitors in relapsed ovarian carcinoma, the pathways of the oncogenetic counseling were modified. Any research for a constitutional alteration of the BRCA1 and BRCA2 genes must be accompanied by an oncogenetic counseling. BRCA testing is recommended from the diagnosis to every woman with an ovarian or fallopian tube or peritoneum of high grade adenocarcinoma, whatever the age at the diagnosis and her family history. In case of sensitive relapse or potential inclusion in a clinical trial and in the absence of preliminary constitutional research, the oncogenetic counseling is organized according to a fast track pathway and a somatic analysis can be realized in parallel...
May 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28625310/mise-%C3%A3-jour-2016-des-recommandations-pour-la-pratique-clinique-de-nice-saint-paul-de-vence-dans-le-cancer-de-l%C3%A2-ovaire-et-du-col-de-l%C3%A2-ut%C3%A3-rus-%C3%A3-un-stade-avanc%C3%A3
#6
Florence Joly, Denis Querleu, Moise Namer, Eric Pujade-Lauraine
UPDATED 2016 RECOMMENDATIONS FOR THE CLINICAL PRACTICE OF NICE/SAINT-PAUL-DE-VENCE IN OVARIAN CANCER AND ADVANCED CERVICAL CANCER: Since the first edition of the 2012-2013 Clinical Practice Recommendations Nice-Saint-Paul for gynecological cancers, the management of ovarian cancer has become more complex with a better definition of histological subtypes of ovarian cancers, the update of the anatomo-clinical classifications, the evolution of the recommended quality criteria for surgery. In addition, the integration of new medical options, such as PARP inhibitors, requires us to review our management of ovarian cnacer patients (including early systematic oncogenetic research of homologous recombination pathway deficiency)...
May 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28614062/brca-mutations-in-the-manifestation-and-treatment-of-ovarian-cancer
#7
REVIEW
Zimin Pan, Xing Xie
BRCA genes are important for the integrity and stability of genetic material and play key roles in repairing DNA breaks via high fidelity homologous recombination. BRCA mutations are known to predispose carriers to gynecological malignancies, accounting for a majority of hereditary OC cases. Known to be lethal, OC is difficult to detect and control. Testing for BRCA mutations is a key step in the risk assessment, prognosis, treatment and prevention of OC and current clinical guidelines recommend BRCA mutation testing for all OCs of epithelial origin...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28610746/a-universal-genetic-testing-initiative-for-patients-with-high-grade-non-mucinous-epithelial-ovarian-cancer-and-the-implications-for-cancer-treatment
#8
Erica M Bednar, Holly D Oakley, Charlotte C Sun, Catherine C Burke, Mark F Munsell, Shannon N Westin, Karen H Lu
OBJECTIVE: Genetic counseling (GC) and germline genetic testing (GT) for BRCA1 and BRCA2 are considered standard of care for patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC). We describe a universal genetic testing initiative to increase the rates of recommendation and acceptance of GC and GT to >80% for patients with HGOC at our institution. METHODS: Data from a consecutive cohort of patients seen in our gynecologic oncology clinics between 9/1/2012 and 8/31/2015 for evaluation of HGOC were retrospectively analyzed...
June 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28601509/olaparib-hydroxamic-acid-derivatives-as-dual-parp-and-hdac-inhibitors-for-cancer-therapy
#9
Zigao Yuan, Shaopeng Chen, Qinsheng Sun, Ning Wang, Dan Li, Shuangshuang Miao, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Olaparib was the first PARP inhibitor approved by the FDA for patients with BRCA-mutated ovarian cancer. Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of olaparib and HDAC inhibitors. Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors. These hybrid compounds showed potent inhibitory activities against PARP1/2 and HDAC1/6 with IC50 values in the nanomolar range. Furthermore, compound P1 exhibited broad-spectrum antiproliferative activities in selected human cancer cell lines...
May 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28588062/secondary-somatic-mutations-restoring-rad51c-and-rad51d-associated-with-acquired-resistance-to-the-parp-inhibitor-rucaparib-in-high-grade-ovarian-carcinoma
#10
Olga Kondrashova, Minh Nguyen, Kristy Shield-Artin, Anna V Tinker, Nelson N H Teng, Maria I Harrell, Michael J Kuiper, Gwo-Yaw Ho, Holly Barker, Maria Jasin, Rohit Prakash, Elizabeth M Kass, Meghan R Sullivan, Gregory J Brunette, Kara A Bernstein, Robert L Coleman, Anne Floquet, Michael Friedlander, Ganessan Kichenadasse, David M O'Malley, Amit M Oza, James X Sun, Liliane Robillard, Lara Maloney, David D L Bowtell, Heidi Giordano, Matthew J Wakefield, Scott H Kaufmann, Andrew D Simmons, Thomas C Harding, Mitch Raponi, Iain A McNeish, Elizabeth M Swisher, Kevin Lin, Clare L Scott
High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC...
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28583748/development-of-parp-inhibitors-in-gynecological-malignancies
#11
REVIEW
Yvonne L E Ang, David S P Tan
PARP inhibitors demonstrate synthetic lethality in tumors with BRCA1/2 mutations and other homologous recombination repair deficiencies by interfering with DNA repair and causing direct toxicity to DNA through PARP trapping. PARP inhibitors have been shown to be beneficial in the treatment of BRCA1/2-mutated ovarian cancers, which has led to a shift in the treatment paradigm of this disease. Further studies to establish the role of PARP inhibitors during earlier stages of treatment are ongoing. The use of PARP inhibitors in other cancers with homologous recombination repair deficiencies, such as breast cancer and prostate cancer, is gradually evolving as well, including their use in the neoadjuvant and adjuvant settings...
March 14, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28569838/usp13-regulates-the-rap80-brca1-complex-dependent-dna-damage-response
#12
Yunhui Li, Kuntian Luo, Yujiao Yin, Chenming Wu, Min Deng, Lei Li, Yuping Chen, Somaira Nowsheen, Zhenkun Lou, Jian Yuan
BRCA1 regulates multiple cellular pathways that maintain genomic stability including cell cycle checkpoints, DNA repair, protein ubiquitination, chromatin remodelling, transcriptional regulation and apoptosis. Receptor-associated protein 80 (RAP80) helps recruit BRCA1 to double-strand breaks (DSBs) through the scaffold protein CCDC98 (Abraxas) and facilitates DNA damage response (DDR). However, the regulation of RAP80-BRCA1 complex is still unclear. Here we report that a deubiquitinase, USP13, regulates DDR by targeting RAP80...
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28561656/whence-high-grade-serous-ovarian-cancer
#13
Elise C Kohn, S Percy Ivy
Our understanding of epithelial ovarian cancer has blossomed, and we now recognize that it is a collection of varied histologic and molecularly different malignancies, many of which may not derive from a true ovarian anatomic precursor. High-grade serous ovarian cancer (HGSOC) is a unique type of epithelial cancer. It is characterized by nearly universal mutation in and dysfunction of p53, genomic instability rather than driver mutations, advanced stage at onset, and probable fallopian tube epithelium origin, with a serous tubal in situ carcinoma precursor...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28546758/distinct-implications-of-different-brca-mutations-efficacy-of-cytotoxic-chemotherapy-parp-inhibition-and-clinical-outcome-in-ovarian-cancer
#14
REVIEW
Robert L Hollis, Michael Churchman, Charlie Gourley
Approximately a fifth of ovarian carcinoma (OC) is associated with inherited germline mutations, most commonly in the DNA repair genes BRCA1 or BRCA2 (BRCA). BRCA1- and BRCA2-associated OCs have historically been described as a single subgroup of OC that displays a distinct set of characteristics termed the "BRCAness" phenotype. The hallmarks of this phenotype are superior clinical outcome and hypersensitivity to platinum-based chemotherapy and poly-(ADP-ribose) polymerase (PARP) inhibitors. However, growing evidence suggests that BRCA1- and BRCA2-associated OCs display distinct characteristics, most notably in long-term patient survival...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28543772/parp-inhibitor-rucaparib-induces-changes-in-nad-levels-in-cells-and-liver-tissues-as-assessed-by-mrs
#15
Gilberto S Almeida, Carlo M Bawn, Martin Galler, Ian Wilson, Huw D Thomas, Suzanne Kyle, Nicola J Curtin, David R Newell, Ross J Maxwell
Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy ((1) H-MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD(+) ) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response...
May 22, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28508305/recent-advances-in-targeting-dna-repair-pathways-for-the-treatment-of-ovarian-cancer-and-their-clinical-relevance
#16
REVIEW
Katsutoshi Oda, Michihiro Tanikawa, Kenbun Sone, Mayuyo Mori-Uchino, Yutaka Osuga, Tomoyuki Fujii
Poly (ADP-ribose) polymerase (PARP) inhibitors have attracted much attention as one of the major molecular-targeted therapeutics for inhibiting DNA damage response. The PARP inhibitor, olaparib, has been clinically applied for treating certain recurrent ovarian cancer patients with BRCA1/2 mutations in Europe and the United States. It was also designated on 24 March 2017 as an orphan drug in Japan for similar clinical indications. In this review, we discuss (i) the prevalence of BRCA1/2 mutations in ovarian cancer, (ii) clinical trials of PARP inhibitors in ovarian cancer, (iii) genetic counseling for hereditary breast and ovarian cancer patients, and (iv) non-BRCA genes that may be associated with homologous recombination deficiency...
May 15, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28505221/combining-pi3k-and-parp-inhibitors-for-breast-and-ovarian-cancer-treatment
#17
R Condorelli, F André
No abstract text is available yet for this article.
June 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28491146/parp-inhibitors-in-ovarian-cancer-evidence-experience-and-clinical-potential
#18
REVIEW
Tarra Evans, Ursula Matulonis
Inhibitors of poly(ADP-ribose) polymerase (PARP) are considered one of the most active and exciting new therapies for the treatment of ovarian cancer. The anticancer activity of PARP inhibitors is based on the DNA repair vulnerability of many ovarian cancer cells, and multiple mechanisms of action of PARP inhibitors have been identified. As single agents, PARP inhibitors have demonstrated their greatest activity in ovarian cancer cells that harbor mutations in BRCA genes. Additionally, recent phase III studies have shown that single-agent PARP inhibitor activity extends beyond BRCA-related cancers and can benefit patients with ovarian cancers that do not have known BRCA mutations, especially when clinical characteristics such as platinum sensitivity and high-grade serous histology are present...
April 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28486465/fda-approves-parp-inhibitor-for-ovarian-cancer
#19
(no author information available yet)
No abstract text is available yet for this article.
May 9, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28482906/foxm1-expression-is-significantly-associated-with-chemotherapy-resistance-and-adverse-prognosis-in-non-serous-epithelial-ovarian-cancer-patients
#20
Renata A Tassi, Paola Todeschini, Eric R Siegel, Stefano Calza, Paolo Cappella, Laura Ardighieri, Moris Cadei, Mattia Bugatti, Chiara Romani, Elisabetta Bandiera, Laura Zanotti, Laura Tassone, Donatella Guarino, Concetta Santonocito, Ettore D Capoluongo, Luca Beltrame, Eugenio Erba, Sergio Marchini, Maurizio D'Incalci, Carla Donzelli, Alessandro D Santin, Sergio Pecorelli, Enrico Sartori, Eliana Bignotti, Franco Odicino, Antonella Ravaggi
BACKGROUND: Epithelial ovarian cancer (EOC) is a spectrum of different diseases, which makes their treatment a challenge. Forkhead box M1 (FOXM1) is an oncogene aberrantly expressed in many solid cancers including serous EOC, but its role in non-serous EOCs remains undefined. We examined FOXM1 expression and its correlation to prognosis across the three major EOC subtypes, and its role in tumorigenesis and chemo-resistance in vitro. METHODS: Gene signatures were generated by microarray for 14 clear-cell and 26 endometrioid EOCs, and 15 normal endometrium snap-frozen biopsies...
May 8, 2017: Journal of Experimental & Clinical Cancer Research: CR
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