keyword
MENU ▼
Read by QxMD icon Read
search

Olaparib

keyword
https://www.readbyqxmd.com/read/29774075/plectin-targeted-liposomes-enhance-the-therapeutic-efficacy-of-a-parp-inhibitor-in-the-treatment-of-ovarian-cancer
#1
Siva Sai Krishna Dasa, Galina Diakova, Ryo Suzuki, Anne M Mills, Michael F Gutknecht, Alexander L Klibanov, Jill K Slack-Davis, Kimberly A Kelly
Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise...
2018: Theranostics
https://www.readbyqxmd.com/read/29767248/combined-treatment-with-pi3k-inhibitor-bkm120-and-parp-inhibitor-olaparib-is-effective-in-inhibiting-the-gastric-cancer-cells-with-arid1a-deficiency
#2
Lin Yang, Guanghai Yang, Yingjun Ding, Yu Huang, Shunfang Liu, Lei Zhou, Wenjie Wei, Jing Wang, Guangyuan Hu
Dual blockade of phosphoinositide 3-kinase (PI3K) and poly(ADP-ribose) polymerase (PARP) has been revealed to be an effective treatment strategy for breast, ovarian and prostate cancer. However, the efficacy of this combination for the treatment of gastric cancer, and potential predictive therapeutic biomarkers remain unclear. Recent evidence suggests that the deficiency of AT-rich interactive domain containing protein 1A (ARID1A), which is a crucial chromatin remodeling gene, sensitizes tumor cells to PI3K and PARP inhibitors...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29765171/risks-and-protective-factors-for-triple-negative-breast-cancer-with-a-focus-on-micronutrients-and-infections
#3
Dagmar Horakova, Katerina Bouchalova, Karel Cwiertka, Ladislav Stepanek, Jana Vlckova, Helena Kollarova
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer (BC) with a poor prognosis. Second, patients cannot benefit from targeted therapy, except for those with BRCA1/2 mutations, for whom poly (ADP-ribose) polymerase (PARP) inhibition therapy using olaparib has recently been approved. As global priorities continue to be epidemiological analysis of BC risk factors and early diagnosis, this review focuses on the risks and protective factors associated with TNBC. A PubMed keyword search for new knowledge on the risks and protective factors for TNBC was carried out...
May 15, 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/29750868/brca-status-does-not-predict-synergism-of-a-carboplatin-and-olaparib-combination-in-high-grade-serous-ovarian-cancer-cell-lines
#4
Yen Ting Shen, James C Evans, Gaetano Zafarana, Christine Allen, Micheline Piquette-Miller
Over 50% of epithelial ovarian cancers express the BRCAness profile that leads to a dysfunctional homologous recombination repair system. The combination of a dysfunctional homologous recombination repair system and a poly (ADP-ribose) polymerase (PARP) inhibitor results in a synthetic lethal phenotype. The PARP inhibitor olaparib, approved as a monotherapy for patients with a germline BRCA mutation, has shown promising results in preclinical studies when combined with DNA damaging agents such as carboplatin...
May 11, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29750420/latest-clinical-evidence-and-further-development-of-parp-inhibitors-in-ovarian-cancer
#5
M R Mirza, S Pignata, J A Ledermann
Background: For several decades, the systemic treatment of ovarian cancer has involved chemotherapy, with the relatively recent addition of anti-angiogenic strategies given with chemotherapy and in the maintenance setting. In the past decade, numerous poly(ADP-ribose) polymerase (PARP)-inhibiting agents have been assessed. Design: We review key trials that have led to the approval of three PARP inhibitors - olaparib, niraparib and rucaparib - as maintenance therapy for platinum-sensitive recurrent ovarian cancer...
May 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29748182/a-pdx-organoid-biobank-of-advanced-prostate-cancers-captures-genomic-and-phenotypic-heterogeneity-for-disease-modeling-and-therapeutic-screening
#6
Michael L Beshiri, Caitlin M Tice, Crystal Tran, Holly M Nguyen, Adam G Sowalsky, Supreet Agarwal, Keith H Jansson, Qi Yang, Kerry A McGowen, Juan Juan Yin, Aian Neil Alilin, Fatima H Karzai, William Dahut, Eva Corey, Kathleen Kelly
PURPOSE: Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models   that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29736741/homologous-recombination-deficiency-and-host-anti-tumor-immunity-in-triple-negative-breast-cancer
#7
REVIEW
M L Telli, D G Stover, S Loi, S Aparicio, L A Carey, S M Domchek, L Newman, G W Sledge, E P Winer
PURPOSE: Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. METHODS: We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection...
May 7, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29731958/main-implications-related-to-the-switch-to-brca-1-2-tumor-testing-in-ovarian-cancer-patients-a-proposal-of-a-consensus
#8
Ettore Capoluongo, Giovanni Scambia, Jean-Marc Nabholtz
Background: Since the approval of the first poly (adenosine diphosphate [ADP]) ribose polymerase inhibitor (PARPi; olaparib [Lynparza™]) for platinum-sensitive relapsed high grade ovarian cancer, with either germline or somatic BRCA1/2 deleterious variants, the strategies for BRCA1/2 are dynamically changing. Along with germline testing within the context of familial or sporadic ovarian cancer, patients are now being referred for BRCA1/2 genetic assay above all for treatment decisions: in this setting tumour BRCA assay can allow to identify an estimated 3-9% of patients with peculiar somatic BRCA1/2 mutations...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29731842/effect-of-rad51c-expression-on-the-chemosensitivity-of-e%C3%AE-myc-p19-arf-cells-and-its-clinical-significance-in-breast-cancer
#9
Shao-Guang Liao, Lu Liu, Ya-Jie Wang
The aim of the present study was to investigate the chemosensitivity to anti-cancer drugs of RAD51 paralog C (RAD51C)-deficient Eμ-Myc p19Arf-/- cells, to detect the expression of RAD51C in breast cancer tissues by immunohistochemistry (IHC), and to explore their association with clinicopathological factors. Eμ-Myc p19Arf-/- cells were stably transfected with retroviruses co-expressing short hairpin-RNA against RAD51C and green fluorescent protein (GFP). A single-cell flow cytometry-based GFP competition assay was used to assess the change in sensitivity to anti-cancer drugs...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29730979/economic-impact-of-olaparib-on-maintenance-treatment-of-patients-with-brca-mutation-positive-platinum-sensitive-relapsing-high-grade-serous-epithelial-ovarian-cancer-in-spain
#10
Laura Delgado-Ortega, Jordi Ginés Rubió, Maria Del Carmen Garcías de España, David Carcedo, Luis Cordero Puentes, Carlota Moya de Alarcón
OBJECTIVE: To estimate the economic impact of the introduction of olaparib in  the Spanish National Health System as maintenance monotherapy in patients  with BRCA-mutation positive high-grade serous ovarian cancer. METHOD: A budget impact model was developed from the Spanish NHS perspective and a time horizon of 5 years for four treatment lines. The model included prevalent and incident patients estimated according to Spanish epidemiological data. Patients moved between treatment lines according to the progression-free survival and overall survival curves  obtained from the respective clinical trials...
May 1, 2018: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/29717476/physiologically-based-pharmacokinetic-modeling-for-olaparib-dosing-recommendations-bridging-formulations-drug-interactions-and-patient-populations
#11
Venkatesh Pilla Reddy, Khanh Bui, Graeme Scarfe, Diansong Zhou, Maria Learoyd
We report physiologically based pharmacokinetic-modeling analyses to determine olaparib (tablet or capsule) drug-drug interactions (DDIs). Verified DDI simulations provided dose recommendations for olaparib co-administration with clinically relevant CYP3A4 modulators to eliminate potential risk to patient safety or olaparib efficacy. When olaparib is given with strong/moderate CYP3A inhibitors, the dose should be reduced to 100/150 mg bid (tablet), and 150/200 mg bid (capsule). Olaparib administration is not recommended with strong/moderate CYP3A inducers...
May 1, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29685880/integrative-kinome-profiling-identifies-mtorc1-2-inhibition-as-treatment-strategy-in-ovarian-clear-cell-carcinoma
#12
Joseph J Caumanns, Katrien Berns, G Bea A Wisman, Rudolf S N Fehrmann, Tushar Tomar, Harry Klip, Gert Jan Meersma, E Marielle Hijmans, Annemiek Gennissen, Evelien W Duiker, Desiree Weening, Hiroaki Itamochi, Roelof Jc Kluin, An K L Reyners, Michael J Birrer, Helga B Salvesen, Ignace Vergote, Els Van Nieuwenhuysen, James D Brenton, Elena I Braicu, Jolanta Kupryjanczyk, Beata Spiewankiewicz, Lorenza Mittempergher, Rene Bernards, Ate G J van der Zee, Steven de Jong
PURPOSE: Advanced stage ovarian clear cell carcinoma (OCCC) is unresponsive to conventional platinum-based chemotherapy. Frequent alterations in OCCC include deleterious mutations in the tumor suppressor ARID1A and activating mutations in the PI3K subunit PIK3CA. In this study, we aimed to identify currently unknown mutated kinases in OCCC patients and test druggability of downstream affected pathways in OCCC models. EXPERIMENTAL DESIGN: In a large set of OCCC patients (n=124), the human kinome (518 kinases) and additional cancer related genes were sequenced and copy number alterations were determined...
April 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29683659/the-identification-of-potent-selective-and-orally-available-inhibitors-of-ataxia-telangiectasia-mutated-atm-kinase-the-discovery-of-azd0156-8-6-3-dimethylamino-propoxy-pyridin-3-yl-3-methyl-1-tetrahydro-2h-pyran-4-yl-1-3-dihydro-2h-imidazo-4-5-c-quinolin-2
#13
Kurt G Pike, Bernard Barlaam, Elaine Cadogan, Andrew Campbell, Yingxue Chen, Nicola Colclough, Nichola L Davies, Camila DeAlmeida, Sébastien L Degorce, Myriam Didelot, Allan Dishington, Richard Ducray, Stephen T Durant, Lorraine A Hassall, Jane L Holmes, Gareth D Hughes, Philip A MacFaul, Keith R Mulholland, Thomas M McGuire, Gilles Ouvry, Martin Pass, Graeme R Robb, Natalie Stratton, Zhenhua Wang, Joanne Wilson, Baochang Zhai, Kang Zhao, Nidal Al-Huniti
ATM inhibitors, such as 7, have demonstrated the anti-tumor potential of ATM inhibition when combined with DNA double strand break-inducing agents in mouse xenograft models. However, the properties of 7 result in a relatively high predicted clinically efficacious dose. In an attempt to minimize attrition during clinical development we sought to identify ATM inhibitors with a low predicted clinical dose (<50 mg) and focussed on strategies to increase both ATM potency and predicted human pharmacokinetic half-life (predominantly through the increase of volume of distribution)...
April 23, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29670134/detection-of-functional-protein-domains-by-unbiased-genome-wide-forward-genetic-screening
#14
Mareike Herzog, Fabio Puddu, Julia Coates, Nicola Geisler, Josep V Forment, Stephen P Jackson
Establishing genetic and chemo-genetic interactions has played key roles in elucidating mechanisms by which certain chemicals perturb cellular functions. In contrast to gene disruption/depletion strategies to identify mechanisms of drug resistance, searching for point-mutational genetic suppressors that can identify separation- or gain-of-function mutations has been limited. Here, by demonstrating its utility in identifying chemical-genetic suppressors of sensitivity to the DNA topoisomerase I poison camptothecin or the poly(ADP-ribose) polymerase inhibitor olaparib, we detail an approach allowing systematic, large-scale detection of spontaneous or chemically-induced suppressor mutations in yeast or haploid mammalian cells in a short timeframe, and with potential applications in other haploid systems...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29669169/genetic-testing-for-hereditary-prostate-cancer-current-status-and-limitations
#15
REVIEW
Jun Tu Zhen, Jamil Syed, Kevin Anh Nguyen, Michael S Leapman, Neeraj Agarwal, Karina Brierley, Xavier Llor, Erin Hofstatter, Brian Shuch
A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. These include breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively), mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and ataxia telangiectasia mutated (ATM)...
April 18, 2018: Cancer
https://www.readbyqxmd.com/read/29664016/the-evolving-landscape-of-predictive-biomarkers-of-response-to-parp-inhibitors
#16
Anish Thomas, Junko Murai, Yves Pommier
Poly(ADP-ribose) polymerase inhibitors (PARPis) are DNA-damaging agents that trap PARP-DNA complexes and interfere with DNA replication. Three PARPis - olaparib, niraparib, and rucaparib - were recently approved by the FDA for the treatment of breast and ovarian cancers. These PARPis, along with 2 others (talazoparib and veliparib), are being evaluated for their potential to treat additional malignancies, including prostate cancers. While lack of PARP-1 confers high resistance to PARPis, it has not been established whether or not the levels of PARP-1 directly correlate with tumor response...
May 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29660759/parp-inhibitors-in-breast-cancer-bringing-synthetic-lethality-to-the-bedside
#17
REVIEW
Anita A Turk, Kari B Wisinski
Individuals with breast and ovarian cancer susceptibility gene 1 (BRCA1) or BRCA2 germline mutations have a significantly increased lifetime risk for breast and ovarian cancers. BRCA-mutant cancer cells have abnormal homologous recombination (HR) repair of DNA. In these tumors, the base excision repair (BER) pathway is important for cell survival. The poly(adenosine diphosphate-ribose) polymerase (PARP) enzymes play a key role in BER, and PARP inhibitors are effective in causing cell death in BRCA-mutant cells while sparing normal cells-a concept called synthetic lethality...
April 16, 2018: Cancer
https://www.readbyqxmd.com/read/29651367/-lazarus-response-to-olaparib-in-a-virtually-chemonaive-breast-cancer-patient-carrying-gross-brca2-gene-deletion
#18
Vladimir M Moiseyenko, Vyacheslav A Chubenko, Fedor V Moiseyenko, Lyudmila A Zagorskaya, Yuliya A Zaytseva, Nataliya E Gesha, Evgeny N Zykov, Valeriya I Ni, Elena V Preobrazhenskaya, Anna P Sokolenko, Evgeny N Imyanitov
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene...
February 4, 2018: Curēus
https://www.readbyqxmd.com/read/29644491/update-on-parp-inhibitors-in-breast-cancer
#19
REVIEW
Alexandra S Zimmer, Mitchell Gillard, Stanley Lipkowitz, Jung-Min Lee
The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer. The US Food and Drug Administration has approved three PARPi (olaparib, rucaparib, and niraparib) so far to treat certain ovarian cancers, including those with gBRCAm and olaparib for treatment of gBRCAm breast cancers. Several PARPi are now under clinical development for breast cancer in the various treatment settings. Recently, two phase III trials of olaparib (OlympiaD) and talazoparib (EMBRACA) demonstrated 3-month progression-free survival improvement with PARPi compared to physician's choice single agent chemotherapy in metastatic gBRCAm breast cancer...
April 11, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29644451/emerging-therapies-in-metastatic-prostate-cancer
#20
REVIEW
Daniel W Sonnenburg, Alicia K Morgans
PURPOSE OF REVIEW: In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. RECENT FINDINGS: Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy...
April 11, 2018: Current Oncology Reports
keyword
keyword
16485
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"