Derivation and Application of Molecular Signatures to Prostate Cancer: Opportunities and Challenges

SIMPLE SUMMARY: Prostate cancer continues to exert a significant public health burden across the globe with hundreds of thousands of new diagnoses per year. There have been many advances in prostate cancer treatment that have dramatically improved the outlook for a lot of patients, especially by targeting a key factor in prostate cancer development called the androgen receptor. However, with increasing of targeted therapies we see a shift in the spectrum of treatment resistance disease. Molecular signatures are essentially maps of the potential for tumor evolution. By analyzing patient and pre-clinical model derived data, we may put together lists of genetic determinants of cancer progression and predict if patients will be prone to develop aggressive disease. In this manuscript we are reviewing some of the ways that these signatures are generated and discuss the advantages and disadvantages of their utility in personalized medicine. ABSTRACT: Prostate cancer is a high-incidence cancer that requires improved patient stratification to ensure accurate predictions of risk and treatment response. Due to the significant contributions of transcription factors and epigenetic regulators to prostate cancer progression, there has been considerable progress made in developing gene signatures that may achieve this. Some of these are aligned to activities of key drivers such as the androgen receptor, whilst others are more agnostic. In this review, we present an overview of these signatures, the strategies for their derivation, and future perspectives on their continued development and evolution.