Results 161 to 170 of about 1,652 (181)

Phase 0 trial of AZD1775 in patients with first-recurrence glioblastoma.

Journal of Clinical Oncology, 2016
2008Background: AZD1775 is a first-in-class Wee1 inhibitor with dual-function as a DNA damage sensitizer (via Cdk1-mediated G2-checkpoint arrest) and as a cytotoxic agent (via Cdk2-mediated DNA-des...
Nader Sanai, Jing Li, Julie Boerner, Harshil Dhruv, Michael E. Berens, Patricia LoRusso   +5 more
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Abstract 862: Sensitization of pancreatic cancer to chemoradiation by the Wee1 inhibitor AZD1775

Cancer Research, 2014
Abstract Gemcitabine-based chemoradiation is standard therapy for locally advanced pancreatic cancer and is associated with an approximately one year median survival. In order to improve the efficacy of this therapy, integration of agents which target the DNA damage response, such as inhibitors of Wee1, is a promising strategy. The goals
Tasneem Kausar, Leslie A. Parsels, Joshua D. Parsels, David Karnak, Mary A. Davis, Jonathan Maybaum, Theodore S. Lawrence, Meredith A. Morgan   +7 more
openaire   +1 more source

Population Pharmacokinetic Modeling of Adavosertib (AZD1775) in Patients with Solid Tumors

The Journal of Clinical Pharmacology
AbstractAdavosertib (AZD1775) is a potent small‐molecule inhibitor of Wee1 kinase. This analysis utilized pharmacokinetic data from 8 Phase I/II studies of adavosertib to characterize the population pharmacokinetics of adavosertib in patients (n = 538) with solid tumors and evaluate the impact of covariates on exposure.
Martin Johnson, Daniel Kaschek, Dana Ghiorghiu, Shankar Lanke, Kowser Miah, Henning Schmidt, Ganesh M. Mugundu   +6 more
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A phase Ib study of AZD1775 and olaparib combination in patients with refractory solid tumors.

Journal of Clinical Oncology, 2016
5562Background: Tumors with G1/S checkpoint deficiencies rely on Wee1 kinase to arrest cell cycle progression at G2/M to repair damaged DNA. AZD1775 is a potent inhibitor of Wee1.
Erika Paige Hamilton, Judy Sing-Zan Wang, Gerald Falchook, Suzanne Fields Jones, Carl Cook, Ganesh Mugundu, Philip John Jewsbury, Mark J. O'Connor, Andrew J Pierce, Bob T. Li, Amit M. Oza, Jeffrey R. Infante, Howard A. Burris, David R. Spigel   +13 more
openaire   +1 more source

Safety, tolerability, and antitumor activity of once-daily Wee-1 inhibitor AZD1775.

Journal of Clinical Oncology, 2018
2587Background: Wee1 tyrosine kinase promotes G2 cell cycle arrest following DNA damage via inactivating phosphorylation of cyclin-dependent kinase 1.
Naoko Takebe, Geraldine Helen O'Sullivan Coyne, Shivaani Kummar, Khanh Tu Do, Ashley Bruns, Lamin Juwara, Mary Flanagan Quinn, Lyndsay Harris, Richard Piekarz, Sheila Ann Prindiville, Elad Sharon, Howard Streicher, Ganesh Mugundu, Jiuping Jay Ji, Deborah Wilsker, Robert J. Kinders, Larry Rubinstein, James H. Doroshow, Alice P. Chen   +18 more
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Phase I trial of AZD1775 (MK1775), a wee1 kinase inhibitor, in patients with refractory solid tumors.

Journal of Clinical Oncology, 2014
2503 Background: Wee1 tyrosine kinase phosphorylates and inactivates Cdk1, causing G2 cell cycle arrest in response to DNA damage.
Khanh Tu Do, Deborah Wilsker, Priya Balasubramanian, Jennifer Zlott, Woondong Jeong, Scott M Lawrence, Robert J. Kinders, Jerry Collins, Alice P. Chen, James H. Doroshow, Shivaani Kummar   +10 more
openaire   +1 more source

Small-molecule-inhibitor of WEE1, AZD1775 as a chemosensitizing agent in acute leukemia, A

2017
Although some patients with acute leukemia have good prognoses, the prognosis of adult and pediatric patients who relapse or cannot tolerate standard chemotherapy is poor. Thus, novel therapies are necessary to improve outcomes in acute leukemia. Conventional chemotherapy is the mainstay of treatment for acute leukemia, and one approach to improving ...
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Phase I study of definitive chemoradiation with gemcitabine and the WEE1 inhibitor AZD1775 in unresectable pancreatic cancer.

Journal of Clinical Oncology, 2017
TPS512 Background: Targeting cell cycle checkpoints has the potential to enhance the efficacy of chemoradiation therapy. Tumor cells commonly have an abnormal G1 checkpoint due to mutations in the p53 pathway making them reliant on the G2 checkpoint to repair DNA damage.
Kyle Clifford Cuneo, Meredith Morgan, Matthew J Schipper, Jonathan Maybaum, Mahmoud Al-Hawary, Diane M. Simeone, Vaibhav Sahai, Mark Zalupski, Theodore Steven Lawrence   +8 more
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Abstract 7872: CDK7 inhibition mitigates AZD1775 resistance via chromatin reprogramming in MYC-MB

Cancer Research
Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children, comprising ∼20% of pediatric brain tumors. MB is a heterogeneous disease, with clinical outcomes heavily influenced by molecular subgroups. Among these, Group 3 MB, characterized by MYC amplification, exhibits the poorest prognosis, with a high ...
Kiara Smart, Bethany Veo, Rajeev Vibhakar   +2 more
openaire   +1 more source

A phase II trial of AZD1775 plus carboplatin-paclitaxel in squamous cell lung cancer (SqCLC).

Journal of Clinical Oncology
8545 Background: In pre-clinical studies, WEE1 inhibitors have displayed synergy with cisplatin in lung cancer cell lines. Adavosertib (AZD1775) is an orally available inhibitor of the WEE1 kinase with platinum-doublet combination RP2D of 225 mg twice daily (BID) on days 1-3 (5 doses) of a 21-day cycle with the most common adverse events being bone ...
Bruna Pellini, Jiannong Li, Michael J Schell, Michael Melendez, Tawee Tanvetyanon, Ben C. Creelan, Alberto Chiappori, Andreas Nicholas Saltos, Eric B. Haura, Michael Rahman Shafique, Trevor Rose, Farah Khalil, Stephanee Smikker, Sam Vafadar, Ashley Sansil, Jessica Wermuth, Milijana Ugrenovic-Petrovic, Alvaro N.A. Monteiro, Uwe Rix, Jhanelle E. Gray   +19 more
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