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Olaparib prostat

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https://www.readbyqxmd.com/read/27875103/diffusion-weighted-imaging-as-a-treatment-response-biomarker-for-evaluating-bone-metastases-in-prostate-cancer-a-pilot-study
#1
Raquel Perez-Lopez, Joaquin Mateo, Helen Mossop, Matthew D Blackledge, David J Collins, Mihaela Rata, Veronica A Morgan, Alison Macdonald, Shahneen Sandhu, David Lorente, Pasquale Rescigno, Zafeiris Zafeiriou, Diletta Bianchini, Nuria Porta, Emma Hall, Martin O Leach, Johann S de Bono, Dow-Mu Koh, Nina Tunariu
Purpose To determine the usefulness of whole-body diffusion-weighted imaging (DWI) to assess the response of bone metastases to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods A phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose) polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance (MR) imaging substudy; the study was approved by the institutional research board, and written informed consent was obtained...
November 22, 2016: Radiology
https://www.readbyqxmd.com/read/27675112/nanoformulation-of-the-parp-inhibitor-olaparib-enables-radiosensitization-of-a-radiation-resistant-prostate-cancer-model
#2
P Baldwin, A L Van De Ven, N Seitzer, S Clohessy, R A Cormack, M Makrigiorgos, P P Pandolfi, S Sridhar
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27600766/evaluation-of-the-radiosensitizing-potency-of-chemotherapeutic-agents-in-prostate-cancer-cells
#3
Colin Rae, Robert J Mairs
PURPOSE: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. Although ionizing radiation is used to treat localized and metastatic prostate cancer, the most efficient use of radiotherapy is yet to be defined. Our purpose was to determine in vitro the potential benefit to be gained by combining radiation treatment with cytotoxic drugs. MATERIALS AND METHODS: Inhibitors of DNA repair and heat shock protein 90 and an inducer of oxidative stress were evaluated in combination with X-radiation for their capacity to reduce clonogenic survival and delay the growth of multicellular tumor spheroids...
October 3, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27428646/parp-inhibitors-in-clinical-use-induce-genomic-instability-in-normal-human-cells
#4
Shuhei Ito, Conleth G Murphy, Ekaterina Doubrovina, Maria Jasin, Mary Ellen Moynahan
Poly(ADP-ribose) polymerases (PARPs) are the first proteins involved in cellular DNA repair pathways to be targeted by specific inhibitors for clinical benefit. Tumors harboring genetic defects in homologous recombination (HR), a DNA double-strand break (DSB) repair pathway, are hypersensitive to PARP inhibitors (PARPi). Early phase clinical trials with PARPi have been promising in patients with advanced BRCA1 or BRCA2-associated breast, ovary and prostate cancer and have led to limited approval for treatment of BRCA-deficient ovary cancer...
2016: PloS One
https://www.readbyqxmd.com/read/27426307/combined-inhibition-of-pi3k-and-parp-is-effective-in-the-treatment-of-ovarian-cancer-cells-with-wild-type-pik3ca-genes
#5
Dong Wang, Chengbo Li, Yuan Zhang, Min Wang, Nan Jiang, Lin Xiang, Ting Li, Thomas M Roberts, Jean J Zhao, Hailing Cheng, Pixu Liu
OBJECTIVE: Combined inhibition of PI3K and PARP has been shown to be effective in the treatment of preclinical models of breast cancer and prostate cancer independent of BRCA or PIK3CA mutational status. However, the knowledge about this combination treatment in ovarian cancer is limited. The aim of this study was to evaluate the therapeutic effect of PI3K inhibitor BKM120 and PARP inhibitor Olaparib on ovarian cancer cell lines bearing wild-type PIK3CA genes. METHODS: We exposed three wild-type PIK3CA ovarian cancer cell lines to a PI3K inhibitor BKM120 and/or a PARP inhibitor Olaparib...
September 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27317574/dna-repair-deficiency-is-common-in-advanced-prostate-cancer-new-therapeutic-opportunities
#6
REVIEW
Mallika Dhawan, Charles J Ryan, Alan Ashworth
UNLABELLED: : Advances in DNA sequencing technology have created a wealth of information regarding the genomic landscape of prostate cancer. It had been thought that BRCA1 and BRCA2 mutations were associated with only a small fraction of prostate cancer cases. However, recent genomic analysis has revealed that germline or somatic inactivating mutations in BRCA1 or BRCA2, or other genes involved in the homologous recombination (HR) pathway of DNA repair collectively occur in as much as 20%-25% of advanced prostate cancers...
August 2016: Oncologist
https://www.readbyqxmd.com/read/27302781/re-dna-repair-defects-and-olaparib-in-metastatic-prostate-cancer
#7
Samir S Taneja
No abstract text is available yet for this article.
April 2016: Journal of Urology
https://www.readbyqxmd.com/read/27302290/re-dna-repair-defects-and-olaparib-in-metastatic-prostate-cancer
#8
Wim P J Witjes
No abstract text is available yet for this article.
July 2016: European Urology
https://www.readbyqxmd.com/read/27139157/preliminary-evaluation-of-prostate-targeted-radiotherapy-using-131-i-mip-1095-in-combination-with-radiosensitising-chemotherapeutic-drugs
#9
Mathias Tesson, Colin Rae, Colin Nixon, John W Babich, Robert J Mairs
OBJECTIVES: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. (131) I-MIP-1095 is a recently developed prostate-specific membrane antigen (PSMA)-targeting, small molecular weight radiopharmaceutical which has anti-tumour activity as a single agent. Our purpose was to determine in vitro the potential benefit to be gained by combining (131) I-MIP-1095 with cytotoxic drug treatments...
July 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/26909613/effective-use-of-pi3k-inhibitor-bkm120-and-parp-inhibitor-olaparib-to-treat-pik3ca-mutant-ovarian-cancer
#10
Dong Wang, Min Wang, Nan Jiang, Yuan Zhang, Xing Bian, Xiaoqing Wang, Thomas M Roberts, Jean J Zhao, Pixu Liu, Hailing Cheng
Recent preclinical studies revealed the efficacy of combined use of PI3K inhibitor BKM120 and PARP inhibitor Olaparib in breast and prostate cancers. The current study investigated the effect of such drug combination on ovarian cancer. Here we showed that combined inhibition of PI3K and PARP effectively synergized to inhibit proliferation, survival and invasion in the majority of ovarian cancer cell lines harboring PIK3CA mutations, including SKOV3, HEYA8, and IGROV1. Mechanistically, combined treatment of PARP and PI3K inhibitors resulted in an exacerbated DNA damage response and more substantially reduced AKT/mTOR signaling when compared to single-agent...
March 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/26658963/olaparib-targets-some-advanced-prostate-cancers
#11
(no author information available yet)
In the phase II TOPARP-A clinical trial, patients with metastatic castrate-resistant prostate cancer who were treated with the PARP inhibitor olaparib lived nearly three times longer without their cancer worsening if their tumors had mutations in at least one of 12 DNA repair genes. However, physicians say that a larger trial is needed to confirm olaparib's effectiveness against the disease before they start routinely sequencing tumors and prescribing the drug.
January 2016: Cancer Discovery
https://www.readbyqxmd.com/read/26510020/dna-repair-defects-and-olaparib-in-metastatic-prostate-cancer
#12
MULTICENTER STUDY
Joaquin Mateo, Suzanne Carreira, Shahneen Sandhu, Susana Miranda, Helen Mossop, Raquel Perez-Lopez, Daniel Nava Rodrigues, Dan Robinson, Aurelius Omlin, Nina Tunariu, Gunther Boysen, Nuria Porta, Penny Flohr, Alexa Gillman, Ines Figueiredo, Claire Paulding, George Seed, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliott, Ursula McGovern, Diletta Bianchini, Jane Goodall, Zafeiris Zafeiriou, Chris T Williamson, Roberta Ferraldeschi, Ruth Riisnaes, Bernardette Ebbs, Gemma Fowler, Desamparados Roda, Wei Yuan, Yi-Mi Wu, Xuhong Cao, Rachel Brough, Helen Pemberton, Roger A'Hern, Amanda Swain, Lakshmi P Kunju, Rosalind Eeles, Gerhardt Attard, Christopher J Lord, Alan Ashworth, Mark A Rubin, Karen E Knudsen, Felix Y Feng, Arul M Chinnaiyan, Emma Hall, Johann S de Bono
BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib. METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day...
October 29, 2015: New England Journal of Medicine
https://www.readbyqxmd.com/read/26310895/quinazolinedione-sirt6-inhibitors-sensitize-cancer-cells-to-chemotherapeutics
#13
Giovanna Sociali, Lauretta Galeno, Marco Daniele Parenti, Alessia Grozio, Inga Bauer, Mario Passalacqua, Silvia Boero, Alessandra Donadini, Enrico Millo, Marta Bellotti, Laura Sturla, Patrizia Damonte, Alessandra Puddu, Claudia Ferroni, Greta Varchi, Claudio Franceschi, Alberto Ballestrero, Alessandro Poggi, Santina Bruzzone, Alessio Nencioni, Alberto Del Rio
The NAD(+)-dependent sirtuin SIRT6 is highly expressed in human breast, prostate, and skin cancer where it mediates resistance to cytotoxic agents and prevents differentiation. Thus, SIRT6 is an attractive target for the development of new anticancer agents to be used alone or in combination with chemo- or radiotherapy. Here we report on the identification of novel quinazolinedione compounds with inhibitory activity on SIRT6. As predicted based on SIRT6's biological functions, the identified new SIRT6 inhibitors increase histone H3 lysine 9 acetylation, reduce TNF-α production and increase glucose uptake in cultured cells...
September 18, 2015: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/25904654/stratifying-prostate-patients-for-olaparib
#14
(no author information available yet)
Data from the phase II TOPARP-A clinical trial indicate that men with metastatic castration-resistant prostate cancer are more likely to respond to the PARP inhibitor olaparib if they have mutations in DNA damage repair genes. The study provides the first data supporting molecular stratification for patients with this disease.
June 2015: Cancer Discovery
https://www.readbyqxmd.com/read/25708226/parp-inhibitors-a-new-era-of-targeted-therapy
#15
REVIEW
Shifalika Tangutoori, Paige Baldwin, Srinivas Sridhar
Personalized medicine seeks to utilize targeted therapies with increased selectivity and efficacy in preselected patient cohorts. One such molecularly targeted therapy is enabled by inhibiting the enzyme poly(ADP-ribose) polymerase (PARP) by small molecule inhibitors in tumors which have a defect in the homologous DNA recombination pathway, most characteristically due to BRCA mutations. Olaparib, a highly potent PARP inhibitor, has recently been the approved for ovarian cancer therapy by the FDA and European commission in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with BRCA1 or BRCA2 mutations...
May 2015: Maturitas
https://www.readbyqxmd.com/read/25616434/olaparib-first-global-approval
#16
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
https://www.readbyqxmd.com/read/25583815/olaparib-effective-in-four-advanced-cancers
#17
(no author information available yet)
In a phase II study, researchers found that the PARP inhibitor olaparib led to stable disease or tumor regressions in patients with advanced breast, ovarian, pancreatic, and prostate cancers who had germline mutations in BRCA1 or BRCA2.
January 2015: Cancer Discovery
https://www.readbyqxmd.com/read/25366685/olaparib-monotherapy-in-patients-with-advanced-cancer-and-a-germline-brca1-2-mutation
#18
MULTICENTER STUDY
Bella Kaufman, Ronnie Shapira-Frommer, Rita K Schmutzler, M William Audeh, Michael Friedlander, Judith Balmaña, Gillian Mitchell, Georgeta Fried, Salomon M Stemmer, Ayala Hubert, Ora Rosengarten, Mariana Steiner, Niklas Loman, Karin Bowen, Anitra Fielding, Susan M Domchek
PURPOSE: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) -associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. PATIENTS AND METHODS: This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy...
January 20, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/25127709/synergistic-loss-of-prostate-cancer-cell-viability-by-coinhibition-of-hdac-and-parp
#19
Olivia S Chao, Oscar B Goodman
UNLABELLED: Tumors with BRCA germline mutations are defective in repairing DNA double-strand breaks (DSB) through homologous recombination (HR) pathways, making them sensitive to PARP inhibitors (PARPi). However, BRCA germline mutations are rare in prostate cancer limiting the ability to therapeutically target these pathways. This study investigates whether histone deacetylase (HDAC) inhibitors (HDACi), reported to modulate DSB repair pathways in sporadic cancers, can downregulate DSB repair pathways and sensitize prostate cancer cells to PARPi...
December 2014: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/24847116/targeting-poly-adp-ribose-polymerase-and-the-c-myb-regulated-dna-damage-response-pathway-in-castration-resistant-prostate-cancer
#20
Likun Li, Wenjun Chang, Guang Yang, Chengzhen Ren, Sanghee Park, Theodoros Karantanos, Styliani Karanika, Jianxiang Wang, Jianhua Yin, Parantu K Shah, Hirayama Takahiro, Masato Dobashi, Wenling Zhang, Eleni Efstathiou, Sankar N Maity, Ana M Aparicio, Elsa M Li Ning Tapia, Patricia Troncoso, Bradley Broom, Lianchun Xiao, Hyun-Sung Lee, Ju-Seog Lee, Paul G Corn, Nora Navone, Timothy C Thompson
Androgen deprivation is the standard treatment for advanced prostate cancer (PCa), but most patients ultimately develop resistance and tumor recurrence. We found that MYB is transcriptionally activated by androgen deprivation therapy or genetic silencing of the androgen receptor (AR). MYB silencing inhibited PCa growth in culture and xenografts in mice. Microarray data revealed that c-Myb and AR shared a subset of target genes that encode DNA damage response (DDR) proteins, suggesting that c-Myb may supplant AR as the dominant regulator of their common DDR target genes in AR inhibition-resistant or AR-negative PCa...
May 20, 2014: Science Signaling
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