Akihiro Yoshida, PhD
Case Western Reserve University and Case Comprehensive Cancer Center
- PhD Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara,
Dr. Yoshida is interested in the molecular mechanisms underlying how the cell cycle is dysregulated in metastatic melanoma. Specifically, key cell cycle regulators, such as cyclin D1 and CDK4, a catalytic partner of cyclin D1, are overexpressed or mutated resulting in constitutive CDK activity in melanoma implying that cyclin D1/CDK4 function is required for development and progression of melanoma. If so, targeting CDK4 or CDK6 is of potential clinical significance. Importantly, CDK4/6 inhibitors have been approved by FDA and under clinical trial. Dr. Yoshida has discovered that CDK4/6 inhibitors induce senescence in vemurafenib, a specific Braf-mutant inhibitor, resistant melanoma and proposed a therapeutic strategy for combination therapy for melanoma patients. He has been continuously working on elucidating the acquired resistant mechanisms of CDK4/6 inhibitors-induced senescence in melanoma by comprehensive analyses such as RNA sequence in vitro, mouse models in vivo, and human clinical samples, which provide avenues for drug combinations to enhance the efficacy of CDK4/6 inhibitors. Based on the concepts that he has developed, he also sets out to start clinical trials with collaborators for melanoma patients.