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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/29736741/homologous-recombination-deficiency-and-host-anti-tumor-immunity-in-triple-negative-breast-cancer
#4
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/29731842/effect-of-rad51c-expression-on-the-chemosensitivity-of-e%C3%AE-myc-p19-arf-cells-and-its-clinical-significance-in-breast-cancer
#5
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/29669169/genetic-testing-for-hereditary-prostate-cancer-current-status-and-limitations
#6
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
#7
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
#8
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
#9
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
#10
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/29593098/administration-of-the-tablet-formulation-of-olaparib-in-patients-with-ovarian-cancer-practical-guidance-and-expectations
#11
REVIEW
Kathleen N Moore, Michael J Birrer
Olaparib is a poly(ADP-ribose) polymerase enzyme inhibitor that is approved for use in patients with advanced ovarian cancer (OC) and genetic BRCA1/2 mutations who have received three or more prior lines of chemotherapy for maintenance treatment of recurrent OC that is in response to platinum-based chemotherapy regardless of BRCA mutation status and for human epidermal growth receptor factor 2-negative metastatic breast cancer with deleterious or suspected deleterious germline BRCA mutations who have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting...
March 28, 2018: Oncologist
https://www.readbyqxmd.com/read/29582690/olaparib-for-the-treatment-of-breast-cancer
#12
Gaia Griguolo, Maria Vittoria Dieci, Valentina Guarneri, PierFranco Conte
Mutations in BRCA1 and BRCA2 genes account for around 2-3% of breast cancer events and more than 10% of triple negative breast cancers. Olaparib (Lynparza®), an orally administered PARP inhibitor, demonstrated clinical benefit in a phase III trial for mutated BRCA-positive HER2 negative metastatic breast cancer. Areas covered: This review gives an overview of available preclinical and clinical data regarding olaparib, including its chemistry, mechanism of action, pharmacokinetics and pharmacodynamics, and evidence supporting antitumor efficacy and safety profile in breast cancer patients...
March 27, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29526802/the-poly-adp-ribose-polymerase-inhibitor-olaparib-induces-up-regulation-of-death-receptors-in-primary-acute-myeloid-leukemia-blasts-by-nf-%C3%AE%C2%BAb-activation
#13
Isabella Faraoni, Francesca Aloisio, Antonio De Gabrieli, Maria Irno Consalvo, Serena Lavorgna, Maria Teresa Voso, Francesco Lo-Coco, Grazia Graziani
Olaparib is a potent orally bioavailable poly(ADP-ribose) polymerase inhibitor (PARPi), approved for BRCA-mutated ovarian and breast cancers. We recently showed that olaparib at clinically achievable concentrations exerts anti-proliferative and pro-apoptotic effects in vitro as monotherapy against primary acute myeloid leukemia (AML) blasts, while sparing normal bone marrow (BM) hematopoietic cells. Since AML expresses low levels of death receptors that may contribute to apoptosis resistance, in this study we investigated whether the anti-leukemia activity of olaparib involves modulation of FAS and TRAIL receptors DR5 and DR4...
June 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29468855/major-clinical-research-advances-in-gynecologic-cancer-in-2017
#14
REVIEW
Dong Hoon Suh, Miseon Kim, Kyung Hun Lee, Keun Yong Eom, Maj Kamille Kjeldsen, Mansoor Raza Mirza, Jae Weon Kim
In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer...
March 2018: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29414021/development-and-validation-of-a-high-performance-liquid-chromatography-method-for-the-quantitation-of-intracellular-parp-inhibitor-olaparib-in-cancer-cells
#15
Pierre Daumar, Robin Dufour, Clémence Dubois, Frédérique Penault-Llorca, Mahchid Bamdad, Emmanuelle Mounetou
Olaparib is a potent PARP inhibitor in clinical use for cancer therapy. A bioanalytical assay was developed and validated for quantitation of intracellular level of olaparib in cells exposed to the drug. The assay involves an optimized and straightforward sample pretreatment with acetonitrile for olaparib solubilization, cell lysis and protein precipitation, and a high performance liquid chromatography (HPLC) method with ultraviolet detection. Several parameters in both the sample preparation and the detection steps were investigated...
April 15, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29382645/first-parp-inhibitor-ok-d-for-breast-cancer
#16
(no author information available yet)
The FDA has approved olaparib, a PARP inhibitor, for use in patients with metastatic breast cancer who also carry a germline BRCA1 or BRCA2 mutation. With the January 12 approval, olaparib becomes the first targeted therapy for patients with breast cancer with mutated BRCA .
March 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29327849/olaparib-for-metastatic-germline-brca-mutated-breast-cancer
#17
Mark Robson, Carsten Goessl, Susan Domchek
No abstract text is available yet for this article.
November 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29327848/olaparib-for-metastatic-germline-brca-mutated-breast-cancer
#18
Steven Narod, Christopher M Booth, William D Foulkes
No abstract text is available yet for this article.
November 2, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29325860/brca2-reversion-mutation-associated-with-acquired-resistance-to-olaparib-in-estrogen-receptor-positive-breast-cancer-detected-by-genomic-profiling-of-tissue-and-liquid-biopsy
#19
Erica L Gornstein, Sara Sandefur, Jon H Chung, Laurie M Gay, Oliver Holmes, Rachel L Erlich, Salil Soman, L Katherine Martin, Andrea V Rose, Philip J Stephens, Jeffrey S Ross, Vincent A Miller, Siraj M Ali, Sibel Blau
No abstract text is available yet for this article.
April 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29251678/novel-poly-adp-ribose-polymerase-inhibitor-combination-strategies-in-ovarian-cancer
#20
Kelly E McCann
PURPOSE OF REVIEW: The recent United States Food and Drug Administration approvals of niraparib and olaparib as maintenance monotherapy for platinum-sensitive, high-grade ovarian cancers independent of BRCA status reflect a willingness to seek indications for poly-ADP-ribose polymerase (PARP) inhibitors beyond cancers with deleterious breast cancer 1 and breast cancer 2 mutations. In this review, I describe the rationale behind current PARP combination clinical trials with chemotherapies, angiogenesis inhibitors, cell cycle checkpoint inhibitors, and inhibitors of the phosphoinositide 3-kinase/AK thymoma/mechanistic target of rapamycin pathway...
February 2018: Current Opinion in Obstetrics & Gynecology
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