The genetic landscapes of urological cancers and their clinical implications in the era of high-throughput genome analysis.

Abstract

With the advent of high-throughput genome analysis, we are increasingly able to sequence and hence understand the pathogenic processes underlying individual cancers. Recently, consortiums such as The Cancer Genome Atlas (TCGA) have performed large-scale projects to this end, providing significant amounts of information regarding the genetic landscapes of several cancers. We performed a narrative review of studies from the TCGA and other major studies. We aimed to summarise data exploring the clinical implications of specific genetic alterations, both prognostically and therapeutically, in four major urological cancers. These were renal cell carcinoma, muscle-invasive bladder cancer/carcinoma, prostate cancer, and testicular germ cell tumours. With these four urological cancers, great strides have been made in the molecular characterisation of tumours. In particular, recent studies have focussed on identifying molecular subtypes of tumours with characteristic genetic alterations and differing prognoses. Other prognostic alterations have also recently been identified, including those pertaining to epigenetics and microRNAs. In regard to treatment, numerous options are emerging for patients with these cancers such as including immune checkpoint inhibition, epigenetic-based treatments, and agents targeting MAPK, PI3K, and DNA repair pathways. There are a multitude of trials underway investigating the effects of these novel agents, the results of which are eagerly awaited. As medicine chases the era of personalised care, it is becoming increasingly important to provide individualised prognoses for patients. Understanding how specific genetic alterations affects prognosis is key for this. It will also be crucial to provide highly targeted treatments against the specific genetics of a patient's tumour. With work performed by the TCGA and other large consortiums, these aims are gradually being achieved. Our review provides a succinct overview of this exciting field that may underpin personalised medicine in urological oncology.