Genomic biomarkers to guide precision radiotherapy in prostate cancer

Abstract

Our ability to prognosticate the clinical course of patients with cancer has historically been limited to clinical, histopathological, and radiographic features. It has long been clear however, that these data alone do not adequately capture the heterogeneity and breadth of disease trajectories experienced by patients. The advent of efficient genomic sequencing has led to a revolution in cancer care as we try to understand and personalize treatment specific to patient clinico-genomic phenotypes. Within prostate cancer, emerging evidence suggests that tumor genomics (e.g., DNA, RNA, and epigenetics) can be utilized to inform clinical decision making. In addition to providing discriminatory information about prognosis, it is likely tumor genomics also hold a key in predicting response to oncologic therapies which could be used to further tailor treatment recommendations. Herein we review select literature surrounding the use of tumor genomics within the management of prostate cancer, specifically leaning toward analyticallyThe Prostate.

Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer

“…In patients with breast cancer for example, analysis of tumor genetics is endorsed by national consensus guidelines, widespread in clinical practice, and frequently impacts choice of treatment. A growing body of evidence suggests that genetic analyses in patients with prostate cancer may improve prognostication, but overall their role remains uncertain (5).…”

Genetics and genomics of prostate cancer and therapeutic implications

“…The next article is by Choudhury, 6 who discusses the prevalence and relevance of alterations in the PTEN–PI3K pathway in advanced prostate cancer, reviews some of the recent clinical agents targeting this pathway, outlines some of the challenges with developing drugs in this context, and discusses some combination strategies (and biomarker selection) for rational therapy development. This is followed by a summary of genomic biomarkers that inform radiotherapeutic approaches, by Sutera et al, 7 who outline some of the most clinically useful DNA‐ and RNA‐based prognostic markers of radiotherapy efficacy, while they also review the emerging field of sensitivity markers for PSMA‐targeted radioligand therapies. Finally, the issue comes to a close with an article by Mizuno et al 8 outlining some novel technologies for studying the epigenome, reviewing the various analytes from which molecular studies can be performed (tissue, circulating tumor DNA, circulating tumor cells, extracellular vesicles), and providing some future directions on where the field will be going moving forward.…”