Poster abstracts
Poster number 27 submitted by Douglas Cheung
Targeting cyclin-dependent kinases in triple negative breast cancer
Douglas G. Cheung (Molecular, Cellular, and Developmental Biology Graduate Program, The Ohio State University), Gianpiero di Leva, Matteo Fassan, Claudia Piovan (Department of Molecular Immunology, Virology and Medical Genetics, The Ohio State University), Krishna Patel, Arpan Kumar, Dorothee Wernicke, Stefano Volinia (Department of Molecular Immunology, Virology and Medical Genetics, The Ohio State University), Marina Ciomei (Business Unit Oncology, Nerviano Medical Sciences), Michela Garofalo (Transcriptional Networks in Lung Cancer, CRUK Manchester Institute), Carlo M. Croce (Department of Molecular Immunology, Virology and Medical Genetics, The Ohio State University)
Abstract:
Triple negative breast cancers (TNBC) are aggressive tumors with dismal prognosis that do not respond to targeted therapies. Here, we tested the efficacy of the multi-cyclin-dependent kinase (CDK) inhibitor PHA-848125 on breast cancer cell lines showing a selectively impaired proliferation in TNBC cells. Oral administration of PHA-848125 to mice bearing TNBC xenotransplanted tumors or genetically engineered mouse model of breast cancer resulted in an inhibition of tumor growth and metastatic progression at tolerable doses. Treatment with a combination of PHA-848125 and cisplatin had a significantly synergistic anti-proliferative and apoptotic effect both in vitro and in vivo. Thus, our preclinical experiments set the rationale for the clinical evaluation of PHA-848125, either alone or in combination with cisplatin.
Keywords: CDK, TNBC, breast cancer