Clinical variability and molecular heterogeneity in prostate cancer

Abstract

Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care.

Figure 1

Illustration depicting prostate cancer heterogeneity. Within the prostate are multiple distinct clones of HgPIN. One of these clones (e.g., one with ETS rearrangement) is adjacent to the primary prostate cancer. Within the primary cancer, a clone with metastatic potential developed which metastasized to the iliac wing. Within this metastasis, multiple subclones developed, one of which has reached a second metastatic site in the sacrum.

Figure 2

Graphical representation of tumor clonal diversity over time and in response to therapy. Multiple clones of HgPIN develop, only a few of which go on to become adenocarcinoma with subsequent clonal evolution throughout progression.