keyword
MENU ▼
Read by QxMD icon Read
search

Veliparib

keyword
https://www.readbyqxmd.com/read/28156017/population-pharmacokinetics-and-site-of-action-exposures-of-veliparib-with-topotecan-plus-carboplatin-in-patients-with-hematological-malignancies
#1
Shailly Mehrotra, Mathangi Gopalakrishnan, Jogarao Gobburu, Jacqueline M Greer, Richard Piekarz, Judith E Karp, Keith Pratz, Michelle A Rudek
AIMS: Veliparib is a potent inhibitor of poly(ADP-ribose) polymerase (PARP) enzyme. The objectives of the analysis were to evaluate the effect of baseline covariates and co-administration of topotecan plus carboplatin (T + C) on pharmacokinetics of veliparib in patients with refractory acute leukemia, and compare veliparib concentration in various biological matrices. METHODS: A population pharmacokinetic model was developed and effect of age, body size indices, sex, creatinine clearance (CrCL), and co-administration of T + C on the pharmacokinetics of veliparib were evaluated...
February 3, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28109627/a-final-report-of-a-phase-i-study-of-veliparib-abt-888-in-combination-with-low-dose-fractionated-whole-abdominal-radiation-therapy-ldfwar-in-patients-with-advanced-solid-malignancies-and-peritoneal-carcinomatosis-with-a-dose-escalation-in-ovarian-and-fallopian
#2
Kim A Reiss, Joseph M Herman, Deborah Armstrong, Marianna Zahurak, Anthony Fyles, Anthony Brade, Michael Milosevic, Laura A Dawson, Angela Scardina, Patricia Fischer, Amy Hacker-Prietz, Robert J Kinders, Lihua Wang, Alice Chen, Sarah Temkin, Naomi Horiba, Lee-Anne Stayner, Lillian L Siu, Nilofer S Azad
BACKGROUND: The combination of low-dose radiation therapy with PARP inhibition enhances anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with ABT-888 in patients with peritoneal carcinomatosis with a dose escalation in ovarian and fallopian cancer patients (OV). METHODS: Patients were treated with veliparib, 40-400mg orally BID on days 1-21 of 3 28-day cycles on 6 dose levels. Dose levels 5 and 6 included only OV patients...
January 18, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28032120/inhibition-of-poly-adp-ribosylation-fails-to-increase-axonal-regeneration-or-improve-functional-recovery-after-adult-mammalian-cns-injury
#3
Xingxing Wang, Yuichi Sekine, Alexandra B Byrne, William B J Cafferty, Marc Hammarlund, Stephen M Strittmatter
After traumatic damage of the brain or spinal cord, many surviving neurons are disconnected, and recovery of function is limited by poor axon regeneration. Recent data have suggested that poly ADP-ribosylation plays a role in limiting axonal regrowth such that inhibition of poly (ADP-ribose) polymerase (PARP) may have therapeutic efficacy for neurological recovery after trauma. Here, we tested systemic administration of the PARP inhibitor, veliparib, and showed effective suppression of PARylation in the mouse CNS...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28031413/let-7-status-is-crucial-for-parp1-expression-in-her2-overexpressing-breast-tumors
#4
Monica E Wielgos, Rajani Rajbhandari, Tiffiny S Cooper, Shi Wei, Susan E Nozell, Eddy S Yang
: HER2+ breast tumors have been shown to express elevated levels of poly (ADPribose) polymerase 1 (PARP1) protein. Yet, the mechanism by which PARP1 is upregulated in HER2+ breast cancer is unknown. Here, knockdown of HER2 (ERBB2) in HER2+ breast cancer cells resulted in a reduction in PARP1 protein. Conversely, ectopic overexpression of HER2 in a non-HER2 overexpressing cell line resulted in increased PARP1 protein. Alterations in HER2 expression had no significant effect on PARP1 transcript levels...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28001384/structural-basis-for-potency-and-promiscuity-in-poly-adp-ribose-polymerase-parp-and-tankyrase-inhibitors
#5
Ann-Gerd Thorsell, Torun Ekblad, Tobias Karlberg, Mirjam Löw, Ana Filipa Pinto, Lionel Trésaugues, Martin Moche, Michael S Cohen, Herwig Schüler
Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective...
December 21, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27998970/a-phase-i-trial-of-paclitaxel-cisplatin-and-veliparib-in-the-treatment-of-persistent-or-recurrent-carcinoma-of-the-cervix-an-nrg-oncology-study-nct-01281852
#6
P H Thaker, R Salani, W E Brady, H A Lankes, D E Cohn, D G Mutch, R S Mannel, K M Bell-McGuinn, P A DiSilvestro, D Jelovac, J S Carter, W Duan, K E Resnick, D S Dizon, C Aghajanian, P M Fracasso
BACKGROUND: Preclinical studies demonstrate poly (ADP-ribose) polymerase (PARP) inhibition augments apoptotic response and sensitizes cervical cancer cells to the effects of cisplatin. Given the use of cisplatin and paclitaxel as first-line treatment for persistent or recurrent cervical cancer, we aimed to estimate the maximum tolerated dose (MTD) of the PARP inhibitor veliparib when added to chemotherapy. PATIENTS AND METHODS: Women with persistent or recurrent cervical carcinoma not amenable to curative therapy were enrolled...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27866910/proteome-wide-profiling-of-clinical-parp-inhibitors-reveals-compound-specific-secondary-targets
#7
Claire E Knezevic, Gabriela Wright, Lily L Remsing Rix, Woosuk Kim, Brent M Kuenzi, Yunting Luo, January M Watters, John M Koomen, Eric B Haura, Alvaro N Monteiro, Caius Radu, Harshani R Lawrence, Uwe Rix
Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a promising class of targeted cancer drugs, but their individual target profiles beyond the PARP family, which could result in differential clinical use or toxicity, are unknown. Using an unbiased, mass spectrometry-based chemical proteomics approach, we generated a comparative proteome-wide target map of the four clinical PARPi, olaparib, veliparib, niraparib, and rucaparib. PARPi as a class displayed high target selectivity. However, in addition to the canonical targets PARP1, PARP2, and several of their binding partners, we also identified hexose-6-phosphate dehydrogenase (H6PD) and deoxycytidine kinase (DCK) as previously unrecognized targets of rucaparib and niraparib, respectively...
December 22, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27831000/targeted-therapies-for-the-treatment-of-non-small-cell-lung-cancer-monoclonal-antibodies-and-biological-inhibitors
#8
Ana P S Silva, Priscila V Coelho, Maristella Anazetti, Patricia U Simioni
The usual treatments for patients with non-small-cell lung cancer (NSCLC), such as advanced lung adenocarcinoma, are unspecific and aggressive, and include lung resection, radiotherapy and chemotherapy. Recently, treatment with monoclonal antibodies and biological inhibitors has emerged as an effective alternative, generating effective results with few side effects. In recent years, several clinical trials using monoclonal antibodies presented potential benefits to NSCLC, and four of them are already approved for the treatment of NSCLC, such as cetuximab, bevacizumab, nivolumab and pembrolizumab...
November 10, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27811964/the-poly-adp-ribose-polymerase-inhibitor-veliparib-and-radiation-cause-significant-cell-line-dependent-metabolic-changes-in-breast-cancer-cells
#9
Vijesh J Bhute, Yan Ma, Xiaoping Bao, Sean P Palecek
Breast tumors are characterized into subtypes based on their surface marker expression, which affects their prognosis and treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in clinical trials, both as single agents and in combination with other chemotherapeutics, in several subtypes of breast cancer patients. Here, we used NMR-based metabolomics to probe cell line-specific effects of the PARP inhibitor Veliparib and radiation on metabolism in three breast cancer cell lines...
November 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27803064/randomized-placebo-controlled-phase-2-study-of-veliparib-in-combination-with-carboplatin-and-paclitaxel-for-advanced-metastatic-non-small-cell-lung-cancer
#10
Suresh S Ramalingam, Normand Blais, Julien Mazieres, Martin Reck, C Michael Jones, Erzsébet Juhász, Laszlo Urban, Sergey Orlov, Fabrice Barlési, Ebenezer Kio, Ulrich Keiholz, Qin Qin, Jiang Qian, Caroline Nickner, Juliann Dziubinski, Hao Xiong, Peter Ansell, Mark D McKee, Vincent Giranda, Vera Gorbunova
PURPOSE: PARP plays an important role in DNA repair. Veliparib, a PARP inhibitor, enhances the efficacy of platinum compounds, and has been safely combined with carboplatin and paclitaxel. The primary endpoint of this phase 2 trial determined whether addition of veliparib to carboplatin and paclitaxel improved PFS in previously untreated advanced/metastatic non-small cell lung cancer patients. EXPERIMENTAL DESIGN: Patients were randomized 2:1 to carboplatin and paclitaxel with either veliparib or placebo...
October 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27739325/a-randomized-phase-ii-study-of-veliparib-with-temozolomide-or-carboplatin-paclitaxel-versus-placebo-with-carboplatin-paclitaxel-in-brca1-2-metastatic-breast-cancer-design-and-rationale
#11
Steven J Isakoff, Shannon Puhalla, Susan M Domchek, Michael Friedlander, Bella Kaufman, Mark Robson, Melinda L Telli, Véronique Diéras, Hyo Sook Han, Judy E Garber, Eric F Johnson, David Maag, Qin Qin, Vincent L Giranda, Stacie P Shepherd
Veliparib is an orally administered poly(ADP-ribose) polymerase inhibitor that is being studied in Phase I-III clinical trials, including Phase III studies in non-small-cell lung cancer, ovarian cancer and breast cancer. Tumor cells with deleterious BRCA1 or BRCA2 mutations are deficient in homologous recombination DNA repair and are intrinsically sensitive to platinum therapy and poly(ADP-ribose) polymerase inhibitors. We describe herein the design and rationale of a Phase II trial investigating whether the addition of veliparib to temozolomide or carboplatin/paclitaxel provides clinical benefit over carboplatin/paclitaxel with placebo in patients with locally recurrent or metastatic breast cancer harboring a deleterious BRCA1 or BRCA2 germline mutation (Trial registration: EudraCT 2011-002913-12, NCT01506609)...
February 2017: Future Oncology
https://www.readbyqxmd.com/read/27716873/the-current-status-of-parp-inhibitors-in-ovarian-cancer
#12
REVIEW
Jennifer McLachlan, Angela George, Susana Banerjee
Recent advances in our understanding of the molecular biology of epithelial ovarian cancer have led to the development of a number of targeted therapies, including poly-ADP-ribose polymerase (PARP) inhibitors. PARP inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations. It has become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this therapeutic approach...
October 13, 2016: Tumori
https://www.readbyqxmd.com/read/27709282/effect-of-veliparib-abt-888-on-cardiac-repolarization-in-patients-with-advanced-solid-tumors-a-randomized-placebo-controlled-crossover-study
#13
Wijith Munasinghe, Sven Stodtmann, Anthony Tolcher, Emiliano Calvo, Michael Gordon, Mathilde Jalving, Judith de Vos-Geelen, Diane Medina, Dennis Bergau, Silpa Nuthalapati, David Hoffman, Stacie Shepherd, Hao Xiong
PURPOSE: Veliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the effect of veliparib on corrected QT interval using Fridericia's formula (QTcF). METHODS: Eligible patients with advanced solid tumors received single-dose oral veliparib (200 mg or 400 mg) or placebo in a 6-sequence, 3-period crossover design. The primary endpoint was the difference in the mean baseline-adjusted QTcF between 400 mg veliparib and placebo (∆∆QTcF) at six post-dose time points...
November 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27686254/the-poly-adp-ribosyl-ation-of-foxo3-mediated-by-parp1-participates-in-isoproterenol-induced-cardiac-hypertrophy
#14
Jing Lu, Renwei Zhang, Huiqi Hong, Zuolong Yang, Duanping Sun, Shuya Sun, Xiaolei Guo, Jiantao Ye, Zhuoming Li, Peiqing Liu
The Forkhead box-containing protein, O subfamily 3 (FoxO3) transcription factor negatively regulates myocardial hypertrophy, and its transcriptional activity is finely conditioned by diverse posttranslational modifications, such as phosphorylation, acetylation, ubiquitination, methylation and glycosylation. Here, we introduce a novel modification of the FoxO3 protein in cardiomyocytes: poly(ADP-ribosyl)ation (PARylation) mediated by poly(ADP-ribose) polymerase-1 (PARP1). This process catalyzes the NAD(+)-dependent synthesis of polymers of ADP-ribose (PAR) and their subsequent attachment to target proteins by PARPs...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27663478/promise-and-limits-of-the-cellsearch-platform-for-evaluating-pharmacodynamics-in-circulating-tumor-cells
#15
REVIEW
Lihua Wang, Priya Balasubramanian, Alice P Chen, Shivaani Kummar, Yvonne A Evrard, Robert J Kinders
Circulating tumor cells (CTCs), which are captured from blood with anti-epithelial cell adhesion molecule (EpCAM) antibodies, have established prognostic value in specific epithelial cancers, but less is known about their utility for assessing patient response to molecularly targeted agents via measurement of pharmacodynamic (PD) endpoints. We discuss the use of CellSearch (Janssen Diagnostics, LLC, Raritan, NJ) CTC isolation technology for monitoring PD response in early phase trials. We present representative data from three clinical trials with the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) suggesting that CTCs can be used to measure PD effects...
August 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27638859/atm-expression-predicts-veliparib-and-irinotecan-sensitivity-in-gastric-cancer-by-mediating-p53-independent-regulation-of-cell-cycle-and-apoptosis
#16
Vinod Vijay Subhash, Shi Hui Tan, Mei Shi Yeo, Fui Leng Yan, Praveen C Peethala, Natalia Liem, Vaidehi Krishnan, Wei Peng Yong
Identification of synthetically lethal cellular targets and synergistic drug combinations is important in cancer chemotherapy as they help to overcome treatment resistance and increase efficacy. The Ataxia Telangiectasia Mutated (ATM) kinase is a nuclear protein that plays a major role in the initiation of DNA repair signaling and cell-cycle check points during DNA damage. Although ATM was shown to be associated with poor prognosis in gastric cancer, its implications as a predictive biomarker for cancer chemotherapy remain unexplored...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27632933/the-parp-inhibitor-abt-888-potentiates-dacarbazine-induced-cell-death-in-carcinoids
#17
Y Somnay, S Lubner, H Gill, J B Matsumura, H Chen
Monoagent DNA-alkylating chemotherapies like dacarbazine are among a paucity of medical treatments for advanced carcinoid tumors, but are limited by host toxicity and intrinsic chemoresistance through the base excision repair (BER) pathway via poly (ADP-ribose) polymerase (PARP). Hence, inhibitors of PARP may potentiate DNA-damaging agents by blocking BER and DNA restoration. We show that the PARP inhibitor ABT-888 (Veliparib) enhances the cytotoxic effects of dacarbazine in carcinoids. Two human carcinoid cell lines (BON and H727) treated with a combination of ABT-888 and dacarbazine resulted in synergistic growth inhibition signified by combination indices <1 on the Chou-Talalay scale...
October 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27551000/a-phase-i-study-of-topotecan-carboplatin-and-the-parp-inhibitor-veliparib-in-acute-leukemias-aggressive-myeloproliferative-neoplasms-and-chronic-myelomonocytic-leukemia
#18
Keith W Pratz, Michelle A Rudek, Ivana Gojo, Mark R Litzow, Michael A McDevitt, Jiuping Ji, Larry M Karnitz, James G Herman, Robert J Kinders, B Douglas Smith, Steven D Gore, Hetty E Carraway, Margaret M Showel, Douglas E Gladstone, Mark J Levis, Hua-Ling Tsai, Gary Rosner, Alice Chen, Scott H Kaufmann, Judith E Karp
Purpose: The PARP inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone.Experimental Design: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPN), and chronic myelomonocytic leukemia (CMML)...
February 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27503200/a-phase-1-study-of-the-parp-inhibitor-veliparib-in-combination-with-temozolomide-in-acute-myeloid-leukemia
#19
Ivana Gojo, Jan H Beumer, Keith W Pratz, Michael A McDevitt, Maria R Baer, Amanda L Blackford, B Douglas Smith, Steven D Gore, Hetty E Carraway, Margaret M Showel, Mark J Levis, Amy E Dezern, Douglas E Gladstone, Jiuping Jay Ji, Lihua Wang, Robert J Kinders, Marie Pouquet, Ismail Ali-Walbi, Michelle A Rudek, Weijie Poh, James G Herman, Larry M Karnitz, Scott H Kaufmann, Alice Chen, Judith E Karp
PURPOSE: In preclinical studies, the PARP inhibitor veliparib enhanced the antileukemic action of temozolomide through potentiation of DNA damage. Accordingly, we conducted a phase 1 study of temozolomide with escalating doses of veliparib in patients with relapsed, refractory acute myeloid leukemia (AML) or AML arising from aggressive myeloid malignancies. EXPERIMENTAL DESIGN: Patients received veliparib [20-200 mg once a day on day 1 and twice daily on days 4-12 in cycle 1 (days 1-8 in cycle ≥2)] and temozolomide [150-200 mg/m(2) daily on days 3-9 in cycle 1 (days 1-5 in cycle ≥2)] every 28 to 56 days...
February 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27488020/treatment-of-breast-cancer-2-brca2-mutant-follicular-dendritic-cell-sarcoma-with-a-poly-adp-ribose-polymerase-parp-inhibitor-a-case-report
#20
Charlotte R Lemech, Rachel Williams, Stephen R Thompson, Brian McCaughan, Melvin Chin
BACKGROUND: Follicular dendritic cell sarcoma is a rare tumour with clinical behaviour covering a spectrum from indolent to aggressive disease. Treatment recommendations are currently based on case reports and small series describing combinations of surgery, chemotherapy and radiotherapy providing the best patient outcomes. Recent knowledge on molecular aberrations in this disease have not yet impacted on therapeutic decisions. CASE PRESENTATION: We describe a case of progressive follicular dendritic cell sarcoma of the lung and pleura, treated based on knowledge of the tumour's molecular aberrations...
August 3, 2016: BMC Research Notes
keyword
keyword
18793
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"