Translational and clinical implications of the genetic landscape of prostate cancer

Abstract

Over the past several years, analyses of data from high-throughput studies have elucidated many fundamental insights into prostate cancer biology. These insights include the identification of molecular alterations and subtypes that drive tumour progression, recurrent aberrations in signalling pathways, the existence of substantial intertumoural and intratumoural heterogeneity, Darwinian evolution in response to therapeutic pressures and the complicated multidirectional patterns of spread between primary tumours and metastatic sites. However, these concepts have not yet been fully translated into clinical tools to improve prognostication, prediction and personalization of treatment of patients with prostate cancer. The current and future clinical implications of 'omics' level knowledge is not only revolutionizing our understanding of prostate cancer biology, but is also shaping ongoing, and future clinical investigations and practice. In this Review, we summarize these advances, and the remaining challenges surrounding tumour heterogeneity and the ability to overcome treatment resistance are also described.

Figure 1. Types and implications of prostate cancer heterogeneity

a ∣ The clinical and anatomical heterogeneity of metastatic prostate cancer fails to capture the immense biological heterogeneity of prostate cancer. b ∣ Intraprostatic/intratumoral heterogeneity, c ∣ Androgen receptor heterogeneity, and d ∣ Darwinian heterogeneity demonstrate clinical strategies and obstacles regarding treatment and diagnosis.