Results 21 to 30 of about 1,652 (181)

WEE1 Inhibition in Combination With Targeted Agents and Standard Chemotherapy in Preclinical Models of Pancreatic Ductal Adenocarcinoma

Frontiers in Oncology, 2021
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with high incidences of p53 mutations. AZD1775 (adavosertib, previously MK-1775) is a small molecule WEE1 inhibitor that abrogates the G2M checkpoint and can potentially synergize with DNA
Sarah J. Hartman, Stacey M. Bagby, Betelehem W. Yacob, Dennis M. Simmons, Morgan MacBeth, Christopher H. Lieu, S. Lindsey Davis, Alexis D. Leal, John J. Tentler, Jennifer R. Diamond, S. Gail Eckhardt, Wells A. Messersmith, Todd M. Pitts   +12 more
doaj   +1 more source

Wee1 Kinase Inhibitor AZD1775 Effectively Sensitizes Esophageal Cancer to Radiotherapy [PDF]

Clinical Cancer Research, 2020
Abstract Purpose: Esophageal cancer is a deadly malignancy with a 5-year survival rate of only 5% to 20%, which has remained unchanged for decades. Esophageal cancer possesses a high frequency of TP53 mutations leading to dysfunctional G1 cell-cycle checkpoint, which likely makes esophageal ...
Linlin Yang, Changxian Shen, Cory J. Pettit, Tianyun Li, Andrew J. Hu, Eric D. Miller, Junran Zhang, Steven H. Lin, Terence M. Williams   +8 more
openaire   +2 more sources

Therapeutic potential of targeting the FLNA-regulated Wee1 kinase in adrenocortical carcinomas. [PDF]

Int J Cancer
What's new? Adrenocortical carcinoma (ACC) is a rare but aggressive cancer of the adrenal gland. In many ACC cases, expression of the cytoskeletal protein filamin A (FLNA) is dramatically reduced; its presence in a tumour is associated with less aggressiveness.
Esposito E, Marra G, Catalano R, Maioli S, Nozza E, Barbieri AM, Hantel C, Di Dalmazi G, Sigala S, Geginat J, Cassinotti E, Baldari L, Palmieri S, Mangone A, Berruti A, Ferrante E, Mantovani G, Peverelli E.   +17 more
europepmc   +2 more sources

PTEN and DNA-PK determine sensitivity and recovery in response to WEE1 inhibition in human breast cancer

eLife, 2020
Inhibition of WEE1 kinase by AZD1775 has shown promising results in clinical cancer trials, but markers predicting AZD1775 response are lacking. Here we analysed AZD1775 response in a panel of human breast cancer (BC) cell lines by global proteome ...
Andrä Brunner, Aldwin Suryo Rahmanto, Henrik Johansson, Marcela Franco, Johanna Viiliäinen, Mohiuddin Gazi, Oliver Frings, Erik Fredlund, Charles Spruck, Janne Lehtiö, Juha K Rantala, Lars-Gunnar Larsson, Olle Sangfelt   +12 more
doaj   +1 more source

Targeting MYC-driven replication stress in medulloblastoma with AZD1775 and gemcitabine

Journal of Neuro-Oncology, 2020
MYC-driven medulloblastomas are highly aggressive childhood tumors with dismal outcomes and a lack of new treatment paradigms. We identified that targeting replication stress through WEE1 inhibition to suppress the S-phase replication checkpoint, combined with the attenuation of nucleotide synthesis with gemcitabine, is an effective strategy to induce ...
Daniel C. Moreira, Sujatha Venkataraman, Apurva Subramanian, John Desisto, Ilango Balakrishnan, Eric Prince, Angela Pierce, Andrea Griesinger, Adam Green, Charles G. Eberhardt, Nicholas K. Foreman, Rajeev Vibhakar   +11 more
openaire   +3 more sources

Effect of food on the pharmacokinetics of the WEE1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors [PDF]

Cancer Chemotherapy and Pharmacology, 2020
Abstract Purpose To support future dosing recommendations, the effect of food on the pharmacokinetics of adavosertib, a first-in-class, small-molecule reversible inhibitor of WEE1 kinase, was assessed in patients with advanced solid tumors. Methods In this Phase I, open-label, randomized, two-period, two-sequence crossover study, the pharmacokinetics
Mats Någård, Mei-Lin Ah-See, Karen So, Marit Vermunt, Fiona Thistlethwaite, Mariette Labots, Patricia Roxburgh, Alain Ravaud, Mario Campone, Liselot Valkenburg-van Iersel, Lone Ottesen, Yan Li, Ganesh Mugundu   +12 more
openaire   +5 more sources

Increased HDAC Activity and c-MYC Expression Mediate Acquired Resistance to WEE1 Inhibition in Acute Leukemia

Frontiers in Oncology, 2020
WEE1 is a cell cycle and DNA damage response kinase that is emerging as a therapeutic target for cancer. AZD1775 is a small molecule inhibitor of WEE1, currently in early phase clinical trials as a single agent and in combination with more conventional ...
Tamara B. Garcia, Rizvan C. Uluisik, Annemie A. van Linden, Kenneth L. Jones, Sujatha Venkataraman, Rajeev Vibhakar, Christopher C. Porter   +6 more
doaj   +1 more source

Polo-like kinase-1, Aurora kinase A and WEE1 kinase are promising druggable targets in CML cells displaying BCR::ABL1-independent resistance to tyrosine kinase inhibitors

Frontiers in Oncology, 2022
In chronic myeloid leukemia (CML), Aurora kinase A and Polo like kinase 1 (PLK1), two serine-threonine kinases involved in the maintenance of genomic stability by preserving a functional G2/M checkpoint, have been implicated in BCR::ABL1-independent ...
Manuela Mancini, Sara De Santis, Cecilia Monaldi, Fausto Castagnetti, Fausto Castagnetti, Annalisa Lonetti, Samantha Bruno, Elisa Dan, Barbara Sinigaglia, Barbara Sinigaglia, Gianantonio Rosti, Michele Cavo, Michele Cavo, Gabriele Gugliotta, Simona Soverini   +14 more
doaj   +1 more source

PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer [PDF]

Molecular Cancer Therapeutics, 2016
Abstract The DNA damage response (DDR) involves a complex network of signaling events mediated by modular protein domains such as the BRCA1 C-terminal (BRCT) domain. Thus, proteins that interact with BRCT domains and are a part of the DDR constitute potential targets for sensitization to DNA-damaging chemotherapy agents.
Ankita, Jhuraney, Nicholas T, Woods, Gabriela, Wright, Lily, Rix, Fumi, Kinose, Jodi L, Kroeger, Elizabeth, Remily-Wood, W Douglas, Cress, John M, Koomen, Stephen G, Brantley, Jhanelle E, Gray, Eric B, Haura, Uwe, Rix, Alvaro N, Monteiro   +13 more
openaire   +2 more sources

Ternary Complex Modeling, Induced Fit Docking and Molecular Dynamics Simulations as a Successful Approach for the Design of VHL-Mediated PROTACs Targeting the Kinase FLT3. [PDF]

Arch Pharm (Weinheim)
An efficient computational approach is presented for designing VHL‐mediated PROTACs by integrating static modeling, induced‐fit docking, and MD simulations. After being validated on four experimental ternary complexes targeting BRD4, SMARCA2, FAK, and WEE1, it was applied to an FLT3‐targeted PROTAC, MA49. MD simulations confirmed stability and provided
Nassar H, Sarnow AC, Celik I, Abdelsalam M, Robaa D, Sippl W.   +5 more
europepmc   +2 more sources