Ana Aparicio is a Professor in the Department of Genitourinary Medical Oncology. She specializes in the treatment of advanced prostate cancer. In order to provide a framework for the study of the androgen indifferent prostate cancers, she defined the ‘aggressive variant prostate cancers’ (AVPC, a subset of prostate cancers of heterogeneous morphologies that share the atypical and virulent clinical behavior and molecular features of the histologically defined androgen receptor-negative small cell or poorly differentiated neuroendocrine prostate carcinomas). Her clinical and translational research focuses on understanding and developing novel therapies for this subset, that has limited therapeutic options and a dismal prognosis. Through a series of prospective clinical trials and parallel studies in preclinical models, she defined a molecular signature for the AVPC that has been linked to resistance to androgen signaling inhibitors and to benefit from platinum-based chemotherapies. The importance of this work lies in that it serves as the foundation for a much needed biologically-based, clinically-relevant molecular classification of prostate cancer that will increase the efficiency of clinical and translational research, permit effective and individualized treatment strategies for the lethal variants and spare patients with non-lethal variants the morbidity of unnecessary treatments.