Results 101 to 110 of about 1,361 (136)

WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study [PDF]

Gynecologic Oncology, 2023
In the first part of this phase II study (NCT01164995), the combination of carboplatin and adavosertib (AZD1775) was shown to be safe and effective in patients with TP53 mutated platinum-resistant ovarian cancer (PROC). Here, we present the results of an additional safety and efficacy cohort and explore predictive biomarkers for resistance and response
Íngrid Hofland
exaly   +6 more sources

Adavosertib (AZD1775) does not prolong the QTc interval in patients with advanced solid tumors: a phase I open-label study

Cancer Chemotherapy and Pharmacology, 2023
Abstract Purpose Adavosertib is a small-molecule, ATP-competitive inhibitor of Wee1 kinase. Molecularly targeted oncology agents have the potential to increase the risk of cardiovascular events, including prolongation of QT interval and associated cardiac arrhythmias.
Mats Nagard, Ganesh M Mugundu
exaly   +4 more sources

Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status [PDF]

Frontiers in Oncology, 2022
Objective: A major challenge in the treatment of platinum-resistant high-grade serous ovarian cancer (HGSOC) is lack of effective therapies. Much of ongoing research on drug candidates relies on HGSOC cell lines that are poorly documented.
Katja Kaipio, Kaisa Huhtinen, Arafat Siddiqui   +2 more
exaly   +4 more sources

Phase I study to assess the effect of adavosertib (AZD1775) on the pharmacokinetics of substrates of CYP1A2, CYP2C19, and CYP3A in patients with advanced solid tumors

Cancer Chemotherapy and Pharmacology, 2023
PURPOSE: Adavosertib may alter exposure to substrates of the cytochrome P450 (CYP) family of enzymes. This study assessed its effect on the pharmacokinetics of a cocktail of probe substrates for CYP3A (midazolam), CYP2C19 (omeprazole), and CYP1A2 ...
Mats Nagard, Ganesh M Mugundu
exaly   +2 more sources

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Efficacy of adavosertib therapy against anaplastic thyroid cancer

Endocrine-Related Cancer, 2021
Wee1 is a kinase that regulates the G2/M progression by the inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease.
Yu-Ling, Lu, Yu-Tung, Huang, Ming-Hsien, Wu, Ting-Chao, Chou, Richard, J Wong, Shu-Fu, Lin   +5 more
openaire   +2 more sources

Phase 1 study of belinostat and adavosertib in patients with relapsed or refractory myeloid malignancies

Cancer Chemotherapy and Pharmacology, 2023
Belinostat is an intravenous histone deacetylase inhibitor with approval for T-cell lymphomas. Adavosertib is a first in class oral Wee1 inhibitor. Preclinical studies of the combination demonstrated synergy in various human acute myeloid leukemia (AML) lines as well as AML xenograft mouse models.This was a phase 1 dose-escalation study of belinostat ...
Steven Grant, Mary Beth Tombes, Ellen Shrader   +2 more
exaly   +3 more sources

Targeting WEE1 by adavosertib inhibits the malignant phenotypes of hepatocellular carcinoma

Biochemical Pharmacology, 2021
Targeting the cell cycle checkpoints and DNA damage response are promising therapeutic strategies for cancer. Adavosertib is a potent inhibitor of WEE1 kinase, which plays a critical role in regulating cell cycle checkpoints. However, the effect of adavosertib on hepatocellular carcinoma (HCC) treatment, including sorafenib-resistant HCC, has not been ...
Jian, Chen, Xing, Jia, Zequn, Li, Wenfeng, Song, Cheng, Jin, Mengqiao, Zhou, Haiyang, Xie, Shusen, Zheng, Penghong, Song   +8 more
openaire   +2 more sources

A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors

Investigational New Drugs, 2023
AbstractAdavosertib selectively inhibits Wee1, which regulates intra-S and G2/M cell-cycle checkpoints. This study investigated dosing schedules for adavosertib monotherapy, determining the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) in patients with advanced solid tumors.Patients received oral adavosertib qd or bid on a 5/9 ...
Esteban Rodrigo Imedio, Suzanne Jones, Gerald Falchook   +2 more
exaly   +3 more sources

Pharmacokinetic and pharmacodynamic analysis of adavosertib in advanced ovarian cancer.

Journal of Clinical Oncology, 2022
5579 Background: Adavosertib (AZD-1775) is a potent small molecule inhibitor of Wee-1, currently in clinical development. In a double-blind, placebo-controlled, phase 2 trial (NCT02151292), adavosertib and gemcitabine significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with recurrent platinum-resistant or ...
Amit M. Oza, Stephanie Lheureux, Ainhoa Madariaga, Mihaela C. Cristea, Gina Mantia-Smaldone, Alexander Olawaiye, Susan Ellard, Johanne I Weberpals, Andrea Elisabeth Wahner Hendrickson, Gini F. Fleming, Stephen Welch, Neesha C. Dhani, Vanessa Speers, Valerie Bowering, Lisa Wang, Wenjiang Zhang, Eric Xueyu Chen   +16 more
openaire   +1 more source

Indicators of Response to the Wee1 Inhibitor Adavosertib in Acute Myeloid Leukemia

Blood, 2023
Wee1 is a nuclear kinase that regulates cell cycle progression by inhibiting Cdk1, which is essential for G2 to M phase transition. Inhibition of Wee1 leads to high Cdk1 activity, causing cells to bypass proper DNA repair at the G2/M checkpoint, resulting in mitotic catastrophe and cell death, plus increased Cdk2 activity, causing ...
Ankita Srivastava, Caroline A. Heckman, Juho Jalmari Miettinen, Olivier Harismendy   +3 more
openaire   +1 more source