keyword
https://read.qxmd.com/read/38534940/the-development-and-testing-of-a-patient-decision-aid-for-individuals-with-homologous-recombinant-proficient-ovarian-cancer-who-are-considering-niraparib-maintenance-therapy
#1
JOURNAL ARTICLE
Laura Hopkins, Mark Carey, Linda Brown, Sabryna McCrea, Mark Milne, Dawne Tokaryk, Dawn Stacey
New treatments for ovarian cancer are available that require trade-offs between progression-free survival and quality of life. The aim of this study was to develop a decision aid for patients with homologous recombinant proficient (HRP) tumors, as the benefit-harm ratio of niraparib needs consideration. This decision aid was created with a systematic and iterative development process based on the Ottawa Decision Support Framework. The decision aid was user-tested for acceptability, usability, and comprehensibility using a survey completed by a sample of patients with ovarian cancer and oncologists...
March 8, 2024: Current Oncology
https://read.qxmd.com/read/38501262/progression-free-survival-and-safety-at-3-5%C3%A2-years-of-follow-up-results-from-the-randomized-phase-3-prima-engot-ov26-gog-3012-trial-of-niraparib-maintenance-treatment-in-patients-with-newly-diagnosed-ovarian-cancer-a-plain-language-summary
#2
REVIEW
Antonio González-Martín, Bhavana Pothuri, Ignace Vergote, Whitney Graybill, Domenica Lorusso, Colleen C McCormick, Gilles Freyer, Floor Backes, Florian Heitz, Andrés Redondo, Richard G Moore, Christof Vulsteke, Roisin E O'Cearbhaill, Izabela A Malinowska, Luda Shtessel, Natalie Compton, Mansoor R Mirza, Bradley J Monk
WHAT IS THIS SUMMARY ABOUT?: This PLSP provides a short summary of an original scientific article that presented results from the PRIMA study after 3.5 years of follow-up time. The original article was published in the European Journal of Cancer in 2023. The PRIMA study included adult patients with newly diagnosed advanced high-risk ovarian cancer whose tumors shrunk or became undetectable after treatment with chemotherapy with or without surgery. The PRIMA study evaluated how well the drug niraparib, also known as Zejula, worked at delaying or preventing ovarian cancer from coming back (recurring) or getting worse (progressing) compared with placebo (a substance with no effects that a doctor gives to a patient instead of a drug)...
March 19, 2024: Future Oncology
https://read.qxmd.com/read/38473293/parp-inhibitors-strategic-use-and-optimal-management-in-ovarian-cancer
#3
REVIEW
Nicholas Hirschl, Wildnese Leveque, Julia Granitto, Valia Sammarco, Mervyns Fontillas, Richard T Penson
Poly (ADP-ribose) polymerase (PARP) inhibitors have become an established part of the anticancer armamentarium. Discovered in the 1980s, PARP inhibitors (PARPis) were initially developed to exploit the presence of BRCA mutations, which disrupt the homologous recombination repair of deoxyribonucleic acid (DNA) via synthetic lethality, an intrinsic vulnerability caused by the cell's dependence on other DNA repair mechanisms for which PARP is an essential contributor. PARPi use expanded with the demonstration of clinical benefit when other mechanisms of high-fidelity DNA damage response were present in cancer cells called homologous repair deficiency (HRD)...
February 25, 2024: Cancers
https://read.qxmd.com/read/38444005/a-real-world-study-of-treatment-patterns-following-disease-progression-in-epithelial-ovarian-cancer-patients-undergoing-poly-adp-ribose-polymerase-inhibitor-maintenance-therapy
#4
JOURNAL ARTICLE
Nan Zhang, Hong Zheng, Yunong Gao, Tong Shu, Hongguo Wang, Yan Cai
BACKGROUND: The efficacy of subsequent therapy after poly-ADP-ribose polymerase (PARP) inhibitor maintenance treatment has raised concerns. Retrospective studies show worse outcomes for platinum-based chemotherapy after progression of PARP inhibitor-maintenance therapy, especially in BRCA-mutant patients. We aimed to describe subsequent therapy in ovarian cancer patients after PARP inhibitor-maintenance therapy and evaluate their response to treatment. We focused on chemotherapy for patients with a progression-free interval (PFI) of ≥ 6 months after prior platinum treatment, based on BRCA status...
March 5, 2024: Journal of Ovarian Research
https://read.qxmd.com/read/38436924/demonstrating-bioequivalence-for-two-dose-strengths-of-niraparib-and%C3%A2-abiraterone-acetate%C3%A2-dual-action-tablets-versus-single-agents-utility-of-clinical-study-data-supplemented-with-modeling-and-simulation
#5
JOURNAL ARTICLE
Alex Yu, Anasuya Hazra, James Juhui Jiao, Peter Hellemans, Anna Mitselos, Hui Tian, Juan Jose Perez Ruixo, Nahor Haddish-Berhane, Daniele Ouellet, Alberto Russu
BACKGROUND AND OBJECTIVE: The combination of niraparib and abiraterone acetate (AA) plus prednisone is under investigation for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC). Regular-strength (RS) and lower-strength (LS) dual-action tablets (DATs), comprising niraparib 100 mg/AA 500 mg and niraparib 50 mg/AA 500 mg, respectively, were developed to reduce pill burden and improve patient experience...
March 4, 2024: Clinical Pharmacokinetics
https://read.qxmd.com/read/38423866/a-relative-bioavailability-bioequivalence-and-food-effect-study-of-niraparib-tablets-in-patients-with-advanced-solid-tumors
#6
JOURNAL ARTICLE
Gerald Falchook, Amita Patnaik, Debra L Richardson, R Donald Harvey, Manish R Sharma, Navid Hafez, Erika Hamilton, Sarina A Piha-Paul, Minal Barve, Trisha Wise-Draper, Manish R Patel, Afshin Dowlati, Joseph Pascuzzo, Shou-Ching Tang, Christina Faltermeier, Izabela A Malinowska, Luda Shtessel, Alina Striha, Elizabeth Potocka
PURPOSE: The poly (ADP-ribose) polymerase inhibitor niraparib is indicated as maintenance treatment in patients with certain subtypes of advanced ovarian cancer, and is being investigated in patients with other solid tumors. Niraparib is available in 100-mg capsules with a starting dosage of 200 or 300 mg/d. This study assessed the relative bioavailability (BA) and bioequivalence (BE) between a 1 × 300-mg tablet relative to 3 × 100-mg niraparib capsules. In addition, the food effect (FE) of a high-fat meal on the pharmacokinetic (PK) properties of tablet-formulated niraparib was investigated...
February 23, 2024: Clinical Therapeutics
https://read.qxmd.com/read/38418162/successful-management-of-ovarian-cancer-progressing-on-olaparib-by-niraparib-following-cytoreduction-a-case-report
#7
JOURNAL ARTICLE
Yuta Endo, Norihito Kamo, Asami Kato, Tetsu Sato, Chikako Okabe, Shigenori Furukawa, Takafumi Watanabe, Shu Soeda
BACKGROUND: Polyadenosine 5'-diphosphoribose polymerase inhibitors (PARP-Is) are novel, effective agents for treating newly diagnosed epithelial ovarian cancer (EOC). However, the effect of PARP-I on the progression of recurrent EOC has not yet been determined. In particular, there is limited evidence regarding retreatment with PARP-I for recurrent EOC that has progressed on PARP-I in the short term. CASE REPORT: A 69-year-old woman with a BRCA1 mutated EOC relapsed five months after starting olaparib maintenance following neoadjuvant chemotherapy and interval debulking surgery...
2024: In Vivo
https://read.qxmd.com/read/38416378/comparison-of-adverse-events-between-parp-inhibitors-in-patients-with-epithelial-ovarian-cancer-a-nationwide-propensity-score-matched-cohort-study
#8
JOURNAL ARTICLE
Gwan Hee Han, Hae-Rim Kim, Hee Yun, Jae-Hoon Kim, Hanbyoul Cho
BACKGROUND: Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce. OBJECTIVE: This study aimed to compare the safety of different PARPi in patients with EOC. PATIENTS AND METHODS: Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment...
February 28, 2024: Targeted Oncology
https://read.qxmd.com/read/38409030/parp-inhibitor-era-in-ovarian-cancer-treatment-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#9
REVIEW
István Baradács, Brigitta Teutsch, Alex Váradi, Alexandra Bilá, Ádám Vincze, Péter Hegyi, Tamás Fazekas, Balázs Komoróczy, Péter Nyirády, Nándor Ács, Ferenc Bánhidy, Balázs Lintner
BACKGROUND: Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer. METHODS: This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022...
February 26, 2024: Journal of Ovarian Research
https://read.qxmd.com/read/38398706/parp-inhibitors-in-metastatic-castration-resistant-prostate-cancer-unraveling-the-therapeutic-landscape
#10
REVIEW
Ashaar Al-Akhras, Chadi Hage Chehade, Arshit Narang, Umang Swami
The treatment landscape of metastatic prostate cancer (mPCa) is rapidly evolving with the recent approvals of poly-ADP ribose polymerase inhibitors (PARPis) as monotherapy or as part of combination therapy with androgen receptor pathway inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC). Already part of the therapeutic armamentarium in different types of advanced cancers, these molecules have shaped a new era in mPCa by targeting genomic pathways altered in these patients, leading to promising responses...
January 30, 2024: Life
https://read.qxmd.com/read/38374474/improved-qsar-models-for-parp-1-inhibition-using-data-balancing-interpretable-machine-learning-and-matched-molecular-pair-analysis
#11
JOURNAL ARTICLE
Anish Gomatam, Bhakti Umesh Hirlekar, Krishan Dev Singh, Upadhyayula Suryanarayana Murty, Vaibhav A Dixit
The poly (ADP-ribose) polymerase-1 (PARP-1) enzyme is an important target in the treatment of breast cancer. Currently, treatment options include the drugs Olaparib, Niraparib, Rucaparib, and Talazoparib; however, these drugs can cause severe side effects including hematological toxicity and cardiotoxicity. Although in silico models for the prediction of PARP-1 activity have been developed, the drawbacks of these models include low specificity, a narrow applicability domain, and a lack of interpretability. To address these issues, a comprehensive machine learning (ML)-based quantitative structure-activity relationship (QSAR) approach for the informed prediction of PARP-1 activity is presented...
February 20, 2024: Molecular Diversity
https://read.qxmd.com/read/38371630/parp-inhibitor-maintenance-treatment-for-newly-diagnosed-ovarian-cancer-patients-a-real-world-study-from-china
#12
JOURNAL ARTICLE
Jinghong Chen, Mengpei Zhang, Kemin Li, Yuanqiong Duan, Jing Zeng, Qingli Li, Danqing Wang, Liang Song, Qintong Li, Rutie Yin
PURPOSE: This study evaluated the efficacy and safety in a real-world population of epithelial ovarian cancer (EOC) treated with poly (ADP-ribose) polymerase inhibitor (PARPi) as first-line maintenance therapy in the largest gynecologic oncology center in Western China. METHODS: This study included patients newly diagnosed EOC who received PARPi as first-line maintenance therapy in West China Second University Hospital from August 1, 2018 to September 31, 2022. The primary endpoints were progression-free survival (PFS) and safety evaluated by Common Terminology Criteria for Adverse Events Version 5...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38370375/proposal-for-classifying-the-emetogenicity-of-oral-anticancer-agents-with-a-focus-on-parp-inhibitors-a-prospective-observational-multicenter-study-jascc-cinv-2002
#13
JOURNAL ARTICLE
Senri Yamamoto, Masami Tsuchiya, Hirotoshi Iihara, Yoh Hayasaki, Kyoko Hori, Yasuo Kumakura, Daichi Watanabe, Hideki Sakai, Satoshi Nakagawa, Akiko Kudoh, Hajime Oishi, Nobuhiro Kado, Makiko Go, Kota Mashima, Takashi Uchida, Moeka Yasue, Akimitsu Maeda, Kimihiro Nishino, Koji Matsumoto, Shinya Sato, Yutaka Ueda, Kensuke Tomio, Katsuhisa Hayashi, Motoki Takenaka, Masahiko Mori, Hiroaki Kajiyama, Yoshimasa Bomoto, Shiro Suzuki, Takuma Ishihara, Akio Suzuki, Masakazu Abe
Background: Olaparib and niraparib (poly adenosine diphosphate [ADP]-ribose polymerase [PARP] inhibitors) have significant antitumor action in patients with ovarian cancer. However, the incidence of nausea and vomiting among patients on these drugs in clinical trials is rather high. There are no guidelines on antiemetic treatment for nausea caused by oral anticancer agents. This study aimed to investigate the incidence of nausea and vomiting caused by PARP inhibitors and the actual situation of antiemetic therapy in patients with gynecologic cancer...
2024: Journal of Cancer
https://read.qxmd.com/read/38362364/cytochrome-p450-inhibitor-inducer-treatment-patterns-among-patients-in-the-united-states-with-advanced-ovarian-cancer-who-were-prescribed-or-were-eligible-for-poly-adenosine-diphosphate-adp-ribose-polymerase-inhibitors-in-the-first-line-maintenance-setting
#14
JOURNAL ARTICLE
Bobbie J Rimel, Dana M Chase, Jessica Perhanidis, Armen A Ghazarian, Ella Xiaoyan Du, Travis Wang, Jinlin Song, Amanda K Golembesky, Jean A Hurteau, Linda Kalilani, Ritu Salani, Bradley J Monk
Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) are metabolized either via carboxylesterase (niraparib) or cytochrome P450 (CYP) enzymes (olaparib and rucaparib). Patients with advanced epithelial ovarian cancer (aOC) who receive concomitant medication metabolized by the CYP system may be at risk of drug-drug interactions impacting PARPi efficacy and tolerability. This study investigated CYP inhibitor/inducer treatment patterns in the first-line maintenance (1Lm) setting for patients with aOC...
February 2024: Gynecologic Oncology Reports
https://read.qxmd.com/read/38360632/primary-fallopian-tube-cancer-followed-by-primary-breast-cancer-in-rad51c-mutation-carrier-treated-with-niraparib-as-first-line-maintenance-therapy-a-case-report
#15
JOURNAL ARTICLE
Hua Yuan, Rong Zhang, Ning Li, Hongwen Yao
Given the rarity of RAD51C mutations, the risk and treatment of metachronous breast cancer after the diagnosis of ovarian cancer in RAD51C mutation carriers is not clear, especially for those who have received PARPi treatment. We report the case of a 65-year-old woman diagnosed with stage IIIC high-grade serous primary fallopian tube cancer. The patient had no family history of breast or ovarian cancer. The patient received three cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin and achieved a complete response...
February 15, 2024: Hereditary Cancer in Clinical Practice
https://read.qxmd.com/read/38336156/a-review-of-poly-adp-ribose-polymerase-1-parp1-role-and-its-inhibitors-bearing-pyrazole-or-indazole-core-for-cancer-therapy
#16
REVIEW
Inês M Bastos, Sandra Rebelo, Vera L M Silva
Cancer is a disease with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. The hallmarks of cancer evidence the acquired cells characteristics that promote the growth of malignant tumours, including genomic instability and mutations, the ability to evade cellular death and the capacity of sustaining proliferative signalization. Poly(ADP-ribose) polymerase-1 (PARP1) is a protein that plays key roles in cellular regulation, namely in DNA damage repair and cell survival. The inhibition of PARP1 promotes cellular death in cells with homologous recombination deficiency, and therefore, the interest in PARP protein has been rising as a target for anticancer therapies...
February 7, 2024: Biochemical Pharmacology
https://read.qxmd.com/read/38325276/health-related-quality-of-life-in-patients-with-newly-diagnosed-advanced-ovarian-cancer-treated-with-niraparib-vs-placebo-results-from-the-phase-3-randomized-prima-engot-ov26-gog-3012-trial
#17
JOURNAL ARTICLE
Bhavana Pothuri, Sileny Han, Dana M Chase, Florian Heitz, Robert A Burger, Lydia Gaba, Linda Van Le, Eva Guerra, David Bender, Jacob Korach, Noelle Cloven, Cristina Churruca, Philippe Follana, Paul DiSilvestro, Jean-François Baurain, Kris Jardon, Carmela Pisano, Ulla Peen, Johanna Mäenpää, Divya Gupta, Emeline Bacqué, Yong Li, Natalie Compton, Jenya Antonova, Bradley J Monk, Antonio González-Martín
OBJECTIVE: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. METHODS: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death...
February 6, 2024: Gynecologic Oncology
https://read.qxmd.com/read/38323288/novel-dual-action-parp-and-microtubule-polymerization-inhibitor-amxi-5001-powerfully-inhibits-growth-of-esophageal-carcinoma-both-alone-and-in-combination-with-radiotherapy
#18
JOURNAL ARTICLE
Nathan R Brand, Yi-Wei Yang, Vivianne Ding, Hannah Dutta, Csaba J Peto, Hassan Lemjabbar-Alaoui, David M Jablons
Esophageal cancer is one of the leading causes of cancer deaths globally with an incidence that is concentrated in specific hot spots in Eastern Asia, the Middle East, Eastern Africa, and South America. 10-year overall survival for patients treated with standard of care chemoradiation followed by surgical resection is below 40% highlighting the need for novel therapeutics to treat this disease. We assessed the effect of AMXI-5001, a novel small molecule poly ADP-Ribose polymerase (PARP) inhibitor and microtubule polymerization inhibitor on tumor growth inhibition in both in-vitro and in-vivo murine models...
2024: American Journal of Cancer Research
https://read.qxmd.com/read/38322025/integrated-transcriptome-and-cell-phenotype-analysis-suggest-involvement-of-parp1-cleavage-hippo-wnt-tgf-%C3%AE-and-mapk-signaling-pathways-in-ovarian-cancer-cells-response-to-cannabis-and-parp1-inhibitor-treatment
#19
JOURNAL ARTICLE
Nurit Shalev, Michelle Kendall, Navin Kumar, Sudeep Tiwari, Seegehalli M Anil, Hagit Hauschner, Savvemala G Swamy, Adi Doron-Faingenboim, Eduard Belausov, Bruce E Kendall, Hinanit Koltai
Introduction: Cannabis sativa is utilized mainly for palliative care worldwide. Ovarian cancer (OC) is a lethal gynecologic cancer. A particular cannabis extract fraction ('F7') and the Poly(ADP-Ribose) Polymerase 1 (PARP1) inhibitor niraparib act synergistically to promote OC cell apoptosis. Here we identified genetic pathways that are altered by the synergistic treatment in OC cell lines Caov3 and OVCAR3. Materials and methods: Gene expression profiles were determined by RNA sequencing and quantitative PCR...
2024: Frontiers in Genetics
https://read.qxmd.com/read/38299539/discovery-of-the-potent-and-selective-atr-inhibitor-camonsertib-rp-3500
#20
JOURNAL ARTICLE
W Cameron Black, Abbas Abdoli, Xiuli An, Anick Auger, Patrick Beaulieu, Michel Bernatchez, Cathy Caron, Amandine Chefson, Sheldon Crane, Mohamed Diallo, Stéphane Dorich, Lee D Fader, Gino B Ferraro, Sara Fournier, Qi Gao, Yelena Ginzburg, Martine Hamel, Yongshuai Han, Paul Jones, Stéphanie Lanoix, Cyrus M Lacbay, Marie-Eve Leclaire, Maayan Levy, Yael Mamane, Amina Mulani, Robert Papp, Charles Pellerin, Audrey Picard, Alexander Skeldon, Kathryn Skorey, Rino Stocco, Miguel St-Onge, Jean-François Truchon, Vouy Linh Truong, Michal Zimmermann, Michael Zinda, Anne Roulston
ATR is a key kinase in the DNA-damage response (DDR) that is synthetic lethal with several other DDR proteins, making it an attractive target for the treatment of genetically selected solid tumors. Herein we describe the discovery of a novel ATR inhibitor guided by a pharmacophore model to position a key hydrogen bond. Optimization was driven by potency and selectivity over the related kinase mTOR, resulting in the identification of camonsertib (RP-3500) with high potency and excellent ADME properties. Preclinical evaluation focused on the impact of camonsertib on myelosuppression, and an exploration of intermittent dosing schedules to allow recovery of the erythroid compartment and mitigate anemia...
February 1, 2024: Journal of Medicinal Chemistry
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