Cancers, Vol. 12, Pages 719: Wee1 Inhibition Enhances the Anti-Tumor Effects of Capecitabine in Preclinical Models of Triple-Negative Breast Cancer

Cancers, Vol. 12, Pages 719: Wee1 Inhibition Enhances the Anti-Tumor Effects of Capecitabine in Preclinical Models of Triple-Negative Breast Cancer Cancers doi: 10.3390/cancers12030719 Authors: Todd M. Pitts Dennis M. Simmons Stacey M. Bagby Sarah J. Hartman Betelehem W. Yacob Brian Gittleman John J. Tentler Diana Cittelly D. Ryan Ormond Wells A. Messersmith S. Gail Eckhardt Jennifer R. Diamond Triple-negative breast cancer (TNBC) is an aggressive subtype defined by lack of hormone receptor expression and non-amplified HER2. Adavosertib (AZD1775) is a potent, small-molecule, ATP-competitive inhibitor of the Wee1 kinase that potentiates the activity of many DNA-damaging chemotherapeutics and is currently in clinical development for multiple indications. The purpose of this study was to investigate the combination of AZD1775 and capecitabine/5FU in preclinical TNBC models. TNBC cell lines were treated with AZD1775 and 5FU and cellular proliferation was assessed in real-time using IncuCyte® Live Cell Analysis. Apoptosis was assessed via the Caspase-Glo 3/7 assay system. Western blotting was used to assess changes in expression of downstream effectors. TNBC patient-derived xenograft (PDX) models were treated with AZD1775, capecitabine, or the combination and assessed for tumor growth inhibition. From the initial PDX screen, two of the four TNBC PDX models demonstrated a better response in the combination treatment than either of the singl...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research