New strategies in prostate cancer: translating genomics into the clinic

Abstract

With the rapidly developing use of next-generation sequencing technologies, there has been a surge in our knowledge of the genomic landscape of prostate cancer and a movement toward developing a molecular subclassification system for the disease. With this new understanding comes great clinical potential, both for the development of biomarkers as well as new therapeutic targets. Herein, we highlight the potential clinical use of recent discoveries and how they fit into our current paradigm. We describe the challenges that lie ahead as we move from genomic sequencing toward routine clinical practice and adopt precision cancer care for patients with prostate cancer.

Figure 1. Molecular sub-classification of prostate cancer

Disease initiation occurs through activation of androgen signaling, complex rearrangements, or other proposed mechanisms, leading to prostate tumors wide clinical heterogeneity and distinct molecular subtypes. Disease progression and resistance to therapy leads to acquisition of new and potentially overlapping molecular alterations.

Figure 2. Proposed Model of Precision Medicine for Prostate Cancer

Patients newly diagnosed with prostate cancer will have their prostate biopsy sequenced using next generation sequencing technologies. Based on molecular subtyping, patients with low risk disease will remain on surveillance and high risk tumors will undergo local therapy with or without the addition of targeted therapy identified through sequencing. At the time of disease progression, metastatic lesions will also be re-biopsied for comprehensive sequencing. Hormonal therapies will be initiated as standard of care, with or without targeted therapy identified through sequencing. When patients progress on therapy, re-biopsy and sequencing will lead to use of targeted therapy based on the molecular profile of the resistant tumor.