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https://www.readbyqxmd.com/read/27821315/current-perspectives-on-recommendations-for-brca-genetic-testing-in-ovarian-cancer-patients
#1
Ignace Vergote, Susana Banerjee, Anne-Marie Gerdes, Christi van Asperen, Christian Marth, Fatima Vaz, Isabelle Ray-Coquard, Dominique Stoppa-Lyonnet, Antonio Gonzalez-Martin, Jalid Sehouli, Nicoletta Colombo
Traditionally, BRCA genetic testing has been undertaken to identify patients and family members at future risk of developing cancer and patients have been referred for testing based on family history. However, the now recognised risk of ovarian cancer (OC) patients, even those with no known family history, harbouring a mutation in BRCA1/2, together with the first poly adenosine diphosphate ribose polymerase inhibitor (PARPi; olaparib [Lynparza]) being licenced for the treatment of BRCA-mutated OC, has led to reconsideration of referral criteria for OC patients...
December 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27705909/parp1-inhibitor-olaparib-lynparza-exerts-synthetic-lethal-effect-against-ligase-4-deficient-melanomas
#2
Małgorzata Czyż, Monika Toma, Anna Gajos-Michniewicz, Kinga Majchrzak, Grazyna Hoser, Janusz Szemraj, Margaret Nieborowska-Skorska, Phil Cheng, Daniel Gritsyuk, Mitchell Levesque, Reinhard Dummer, Tomasz Sliwinski, Tomasz Skorski
Cancer including melanoma may be ''addicted" to double strand break (DSB) repair and targeting this process could sensitize them to the lethal effect of DNA damage. PARP1 exerts an important impact on DSB repair as it binds to both single- and double- strand breaks. PARP1 inhibitors might be highly effective drugs triggering synthetic lethality in patients whose tumors have germline or somatic defects in DNA repair genes. We hypothesized that PARP1-dependent synthetic lethality could be induced in melanoma cells displaying downregulation of DSB repair genes...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27422301/safety-and-tolerability-of-the-olaparib-tablet-formulation-in-japanese-patients-with-advanced-solid-tumours
#3
Kan Yonemori, Kenji Tamura, Makoto Kodaira, Koshi Fujikawa, Tamotsu Sagawa, Taito Esaki, Tsuyoshi Shirakawa, Fumihiko Hirai, Yuki Yokoi, Toshio Kawata, Ben Hatano, Yasuo Takahashi
PURPOSE: This was the first Phase I study to assess the safety and tolerability of the tablet formulation of olaparib (Lynparza™), an oral poly(ADP-ribose) polymerase inhibitor, in Japanese patients with advanced solid tumours. The pharmacokinetic profile and antitumour activity of olaparib tablets were also assessed. METHODS: In this open-label, multicentre study (D081BC00001; NCT01813474), a single dose of olaparib (200 or 300 mg, tablets) was administered on day 1, followed 48 h afterwards by multiple dosing (200 or 300 mg twice daily [bid]) for 28-day cycles...
September 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27385701/olaparib-for-the-treatment-of-brca-mutated-advanced-ovarian-cancer
#4
REVIEW
Marklie Munroe, Jill Kolesar
PURPOSE: The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of olaparib, a first-in-class treatment for advanced treatment-refractory ovarian cancer, are reviewed. SUMMARY: Olaparib (Lynparza, AstraZeneca) is an oral inhibitor of poly(ADP-ribose) polymerase (PARP) proteins that play a key role in DNA repair and genomic stability. Olaparib is indicated for use in treating certain patients with advanced, recurrent ovarian cancer who have mutations of the breast cancer 1 gene (BRCA1) or breast cancer 2 gene (BRCA2)...
July 15, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27267353/incorporating-parp-inhibitors-into-clinical-routine-a-tailored-treatment-strategy-to-tackle-ovarian-cancer
#5
E De Jaeghere, K Vandecasteele, K Claes, A Makar, P Tummers, V Cocquyt, H Denys
DNA repair mechanisms play a key role in oncogenesis and cancer progression in women with BRCA mutation-positive (BRCAm) ovarian cancer (OC). The BRCA1/2 and poly(ADP-ribose) polymerase (PARP) proteins are considered the foremost mediators among the various components of double-strand and single-strand repair, respectively. A series of new therapeutic drugs that target PARP have been developed for BRCAm OC. This class of agents provokes tumour-specific cytotoxicity with minimal side effects by inducing synthetic lethality, of which they are the first clinical example...
May 31, 2016: Acta Clinica Belgica
https://www.readbyqxmd.com/read/27062051/olaparib-maintenance-therapy-in-patients-with-platinum-sensitive-relapsed-serous-ovarian-cancer-and-a-brca-mutation-overall-survival-adjusted-for-postprogression-poly-adenosine-diphosphate-ribose-polymerase-inhibitor-therapy
#6
Ursula A Matulonis, Philipp Harter, Charlie Gourley, Michael Friedlander, Ignace Vergote, Gordon Rustin, Clare Scott, Werner Meier, Ronnie Shapira-Frommer, Tamar Safra, Daniela Matei, Anitra Fielding, Stuart Spencer, David Parry, Lynda Grinsted, Jonathan A Ledermann
BACKGROUND: Maintenance treatment with the oral poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor olaparib (Lynparza) in Study 19 (study number, D0810C00019; ClinicalTrials.gov identifier, NCT00753545) significantly improved progression-free survival in comparison with a placebo for patients with platinum-sensitive, relapsed serous ovarian cancer with a BRCA1/2 mutation (BRCAm), but an interim analysis revealed no statistically significant overall survival (OS) benefit. However, 23% of the patients receiving the placebo switched to a PARP inhibitor after progression...
June 15, 2016: Cancer
https://www.readbyqxmd.com/read/26961146/olaparib-monotherapy-in-patients-with-advanced-relapsed-ovarian-cancer-and-a-germline-brca1-2-mutation-a-multistudy-analysis-of-response-rates-and-safety
#7
U A Matulonis, R T Penson, S M Domchek, B Kaufman, R Shapira-Frommer, M W Audeh, S Kaye, L R Molife, K A Gelmon, J D Robertson, H Mann, T W Ho, R L Coleman
BACKGROUND: The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy. PATIENTS AND METHODS: This analysis evaluated pooled data from two phase I trials [NCT00516373 (study 2); NCT00777582 (study 24)] and four phase II trials [NCT00494442 (study 9); NCT00628251 (study 12); NCT00679783 (study 20); NCT01078662 (study 42)] that recruited women with relapsed ovarian, fallopian tube or peritoneal cancer...
June 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/26938702/olaparib-lynparza-for-advanced-ovarian-cancer
#8
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
February 29, 2016: Medical Letter on Drugs and Therapeutics
https://www.readbyqxmd.com/read/26779812/blocking-c-met-mediated-parp1-phosphorylation-enhances-anti-tumor-effects-of-parp-inhibitors
#9
Yi Du, Hirohito Yamaguchi, Yongkun Wei, Jennifer L Hsu, Hung-Ling Wang, Yi-Hsin Hsu, Wan-Chi Lin, Wen-Hsuan Yu, Paul G Leonard, Gilbert R Lee, Mei-Kuang Chen, Katsuya Nakai, Ming-Chuan Hsu, Chun-Te Chen, Ye Sun, Yun Wu, Wei-Chao Chang, Wen-Chien Huang, Chien-Liang Liu, Yuan-Ching Chang, Chung-Hsuan Chen, Morag Park, Philip Jones, Gabriel N Hortobagyi, Mien-Chie Hung
Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as promising therapeutics for many diseases, including cancer, in clinical trials. One PARP inhibitor, olaparib (Lynparza, AstraZeneca), was recently approved by the FDA to treat ovarian cancer with mutations in BRCA genes. BRCA1 and BRCA2 have essential roles in repairing DNA double-strand breaks, and a deficiency of BRCA proteins sensitizes cancer cells to PARP inhibition. Here we show that the receptor tyrosine kinase c-Met associates with and phosphorylates PARP1 at Tyr907 (PARP1 pTyr907 or pY907)...
February 2016: Nature Medicine
https://www.readbyqxmd.com/read/26669452/the-development-of-parp-inhibitors-in-ovarian-cancer-from-bench-to-bedside
#10
REVIEW
Yvette Drew
The nuclear enzyme poly (ADP-ribose) polymerase (PARP) represents an important novel target in the treatment of ovarian cancer. This article charts over 50 years of research from the discovery of the first PARP enzyme in 1963, to the approval and licensing in 2015 of the first PARP inhibitor, olaparib (Lynparza), in the treatment of BRCA-mutated ovarian cancer.
December 15, 2015: British Journal of Cancer
https://www.readbyqxmd.com/read/26590714/targeting-the-dna-damage-response-in-cancer
#11
REVIEW
Mark J O'Connor
An underlying hallmark of cancers is their genomic instability, which is associated with a greater propensity to accumulate DNA damage. Historical treatment of cancer by radiotherapy and DNA-damaging chemotherapy is based on this principle, yet it is accompanied by significant collateral damage to normal tissue and unwanted side effects. Targeted therapy based on inhibiting the DNA damage response (DDR) in cancers offers the potential for a greater therapeutic window by tailoring treatment to patients with tumors lacking specific DDR functions...
November 19, 2015: Molecular Cell
https://www.readbyqxmd.com/read/26424664/concepts-and-molecular-aspects-in-the-polypharmacology-of-parp-1-inhibitors
#12
REVIEW
Daniela Passeri, Emidio Camaioni, Paride Liscio, Paola Sabbatini, Martina Ferri, Andrea Carotti, Nicola Giacchè, Roberto Pellicciari, Antimo Gioiello, Antonio Macchiarulo
Recent years have witnessed a renewed interest in PARP-1 inhibitors as promising anticancer agents with multifaceted functions. Particularly exciting developments include the approval of olaparib (Lynparza) for the treatment of refractory ovarian cancer in patients with BRCA1/2 mutations, and the increasing understanding of the polypharmacology of PARP-1 inhibitors. The aim of this review article is to provide the reader with a comprehensive overview of the distinct levels of the polypharmacology of PARP-1 inhibitors, including 1) inter-family polypharmacology, 2) intra-family polypharmacology, and 3) multi-signaling polypharmacology...
June 20, 2016: ChemMedChem
https://www.readbyqxmd.com/read/26292709/bracanalysis-cdx-as-a-companion-diagnostic-tool-for-lynparza
#13
REVIEW
Camille C Gunderson, Kathleen N Moore
Lynparza and its companion diagnostic test, BRACAnalysis were approved by the US FDA in December 2014 for recurrent ovarian cancer in women with a germline BRCA mutation. Women with a deleterious BRCA mutation are predisposed to ovarian cancer due to deficient homologous recombination repair. Inhibition of the PARP enzyme forces use of an alternate error-prone pathway for repair; PARP trapping is another mechanism utilized that blocks cellular replication by trapping inactivated PARP onto single-stranded DNA breaks...
2015: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/26272246/bracanalysis-cdx-as-a-companion-diagnostic-tool-for-lynparza
#14
Camille C Gunderson, Kathleen N Moore
Lynparza and its companion diagnostic test, BRACAnalysis were approved by the US FDA in December 2014 for recurrent ovarian cancer in women with a germline BRCA mutation. Women with a deleterious BRCA mutation are predisposed to ovarian cancer due to deficient homologous recombination repair. Inhibition of the PARP enzyme forces use of an alternate error-prone pathway for repair; PARP trapping is another mechanism utilized that blocks cellular replication by trapping inactivated PARP onto single-stranded DNA breaks...
August 13, 2015: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/26187614/fda-approval-summary-olaparib-monotherapy-in-patients-with-deleterious-germline-brca-mutated-advanced-ovarian-cancer-treated-with-three-or-more-lines-of-chemotherapy
#15
REVIEW
Geoffrey Kim, Gwynn Ison, Amy E McKee, Hui Zhang, Shenghui Tang, Thomas Gwise, Rajeshwari Sridhara, Eunice Lee, Abraham Tzou, Reena Philip, Haw-Jyh Chiu, Tiffany K Ricks, Todd Palmby, Anne Marie Russell, Gaetan Ladouceur, Elimika Pfuma, Hongshan Li, Liang Zhao, Qi Liu, Rajesh Venugopal, Amna Ibrahim, Richard Pazdur
On December 19, 2014, the FDA approved olaparib capsules (Lynparza; AstraZeneca) for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. The BRACAnalysis CDx (Myriad Genetic Laboratories, Inc.) was approved concurrently. An international multicenter, single-arm trial enrolled 137 patients with measurable gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy...
October 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26051946/safety-evaluation-of-olaparib-for-treating-ovarian-cancer
#16
REVIEW
Stephanie Lheureux, Valerie Bowering, Katherine Karakasis, Amit M Oza
INTRODUCTION: Olaparib (Lynparza®) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor that has become the first 'personalized' therapy available for patients with BRCA mutation-positive ovarian cancer (OC). A capsule formulation of the drug has recently received approval for use in this population for platinum-sensitive recurrent disease for maintenance therapy following platinum-based chemotherapy in Europe and as third- or fourth-line platinum-sensitive therapy in the USA...
August 2015: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/25899311/olaparib-a-review-of-its-use-as-maintenance-therapy-in-patients-with-ovarian-cancer
#17
REVIEW
James E Frampton
Olaparib (Lynparza™) is a first-in-class, orally-active, small molecule, poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. In the EU, the capsule formulation of olaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive, relapsed, BRCA-mutated (germline and/or somatic), high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy...
April 2015: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/25873776/pharmaceutical-approval-update
#18
Kunj Gohil
Nivolumab (Opdivo) for unresectable or metastatic melanoma; ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak) for hepatitis C virus infection; and olaparib (Lynparza) for ovarian cancer.
March 2015: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/25757679/olaparib-an-oral-parp-1-and-parp-2-inhibitor-with-promising-activity-in-ovarian-cancer
#19
REVIEW
Camille C Gunderson, Kathleen N Moore
Olaparib (Lynparza™; AZD2281) is a potent PARP-1 and PARP-2 inhibitor with biologic activity in ovarian cancer as well as other solid tumors. It has been tested in Phase I and II trials and has single-agent activity in both germline BRCA mutated and sporadic ovarian cancer. Phase III trials assessing the efficacy of olaparib in the maintenance setting following first line and platinum-sensitive recurrence are underway for patients with a germline BRCA mutation, given the inherent molecular compatibility with the drug's mechanism of action...
2015: Future Oncology
https://www.readbyqxmd.com/read/25616434/olaparib-first-global-approval
#20
REVIEW
Emma D Deeks
Olaparib (Lynparza™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by AstraZeneca for the treatment of solid tumours. The primary indication that olaparib is being developed for is BRCA mutation-positive ovarian cancer. A capsule formulation of the drug has received approval for use in this setting in the EU and USA, and a tablet formulation is in global phase III trials (including in the USA, EU, Australia, Brazil, Canada, China, Israel, Japan, Russia and South Korea)...
February 2015: Drugs
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