LABORATORY RESEARCH AZD9496: An Oral Estrogen Receptor Inhibitor that Blocks the Growth of ER-positive and ESR1 Mutant Breast Tumors in Preclinical Models Investigators report the identification and characterization of AZD9496, a non-steroidal small molecule inhibitor of estrogen receptor (ER) α which is a potent and selective antagonist and down-regulator of ERα in vitro and in vivo in ER-positive models of breast cancer. [Cancer Res] Full Article | Abstract Early Adaptation and Acquired Resistance to CDK4/6 Inhibition in Estrogen Receptor-Positive Breast Cancer Scientists report that estrogen receptor-positive breast cancer cells can adapt quickly to CDK4/6 inhibition and evade cytostasis, in part, via noncanonical cyclin D1-CDK2-mediated S-phase entry. [Cancer Res] Abstract DS-8201a, a Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Anti-Tumor Efficacy with Differentiation from T-DM1 In vitro and in vivo pharmacological activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft models. The mechanism of action for the efficacy was also evaluated. [Clin Cancer Res] Abstract Trop-2 Induces Tumor Growth through Akt and Determines Sensitivity to Akt Inhibitors Trop-2 and Akt expression was shown to be tightly coordinated in human breast cancers, with virtual overlap with Akt activation profiles at T308 and S473, consistent with functional interaction in vivo. Akt allosteric inhibitors were shown to only block the growth of Trop-2-expressing tumor cells, both in vitro and in preclinical models, being ineffective on Trop-2-null cells. [Clin Cancer Res] Abstract Targeting the Chromatin Remodeling Enzyme BRG1 Increases the Efficacy of Chemotherapy Drugs in Breast Cancer Cells Researchers demonstrated that knockdown of brahma related gene product 1 (BRG1) sensitized triple negative breast cancer cells to chemotherapeutic drugs used to treat breast cancer. [Oncotarget] Full Article Lysine Demethylase 2A Promotes Stemness and Angiogenesis of Breast Cancer by Upregulating Jagged1 The authors showed that expression of lysine demethylase 2A (KDM2A) is markedly increased in human breast cancer and its overexpression is associated with tumor progression and poor prognosis. Gene set enrichment analysis revealed that inhibition of KDM2A down-regulates angiogenic genes with concurrent reduction of Jagged1, NOTCH1 and HEY1 in the NOTCH signaling. [Oncotarget] Full Article Silencing of Prrx1b Suppresses Cellular Proliferation, Migration, Invasion and Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Scientists found that paired-related homeobox 1b (Prrx1b) was significantly up-regulated in triple-negative breast cancer and associated with tumor size and vascular invasion of breast cancer. Silencing of Prrx1b suppressed the proliferation, migration and invasion of basal-like cancer cells. [J Cell Mol Med] Full Article CLINICAL RESEARCH Efficacy and Safety of Leuprorelin Acetate 6-Month Depot, TAP-144-SR (6M), in Combination with Tamoxifen in Postoperative, Premenopausal Patients with Hormone Receptor-Positive Breast Cancer: A Phase III, Randomized, Open-Label, Parallel-Group Comparative Study Researchers assessed the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer. [Breast Cancer] Full Article |