Editorial: Biomarker and translational prostate cancer research

The existing clinical biomarkers for prostate cancer (PCa) are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid overtreatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two-thirds of the biopsies performed are still unnecessary. Thus, the discovery of noninvasive PCa biomarkers remains an urgent unmet medical need. Once metastasized, there is still no curative therapy. A better understanding of sustained androgen receptor signalling in castration resistant prostate cancer (CRPC) has now led to the development of more effective therapies. We need a better understanding of the molecular and cellular aspects of prostate carcinogenesis and progression. Identification of cancer initiating cells and therapies against these populations is a promising way forward to fight this disease.

Clinical application of biomarkers in prostate cancer in men with metabolic syndrome project: Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in diagnosing localised prostate cancer

Localised prostate cancer is a heterogenous disease and a multi-modal approach is required to accurately diagnose and stage the disease. Whilst the use of magnetic resonance imaging (MRI) has become more common, small volume and multi-focal disease are oft en diffi cult to characterise. Prostate specifi c membrane antigen is a cell surface protein, which is expressed in nearly all prostate cancer cells. Its expression is signifi cantly higher in high grade prostate cancer cells. In this study, we compare multi-parametric magnetic resonance imaging and 68-Gallinium-PSMA PET with whole-mount pathology of the prostate to evaluate the applicability of multiparameteric (MP) MRI and 68Ga-PSMA PET in detecting and locating tumour foci in patients with localised prostate cancer.

Characterisation of novel primary tumour derived epithelial prostate cancer cell lines

Current translational and basic prostate cancer research is limited by the number of cell lines that truly reflect the spectrum of disease progression, with most commonly used cell lines being derived from metastatic lesions. There are essentially no prostate cancer cell lines derived from primary tumours or localised disease in wide use.

A multiple nucleotide length polymorphism (MNLP) mediates androgen regulation of IRX4 in prostate cancer

Androgens and the androgen receptor (AR) play a crucial role in the initiation and progression of prostate cancer (PCa), regulating the expression of many PCa risk-associated genes. Iroquois Homeobox 4 (IRX4) has been recently identified with PCa risk and overexpressed in PCa. We observed a down-regulation of IRX4 expression in the cells undergoing epithelial to mesenchymal transition, suggesting its potential role in PCa progression and aim to delineate the androgenmediated regulation of IRX4 in PCa.

Modulation of protease expression in prostate cancer cells after androgen deprivation

Understanding mechanisms associated with the emergence of castration resistant prostate cancer cells (CRPC) after androgen deprivation therapy (ADT) is essential to create new therapeutic agents to counteract this aggressive form of prostate cancer (PCa). Because proteases are involved in almost all cancer associated mechanisms such as cell proliferation, invasion and metastasis, we are interested in their modulation in PCa after ADT and their involvement in CRPC.

Extracellular vesicles mediate paracrine signalling in androgen deprived prostate cancer

The androgen receptor (AR) is the main therapeutic target for advanced prostate cancer (PCa). Current treatments have focused on inhibiting the transcriptional activity of the AR, however androgens can also induce non-genomic effects by facilitating the initiation of kinase signaling cascades in PCa. Cells, including PCa, secrete extracellular vesicles (EV), which are able to mediate communication between cells and can also contribute towards these processes.

A 3D in vitro model reflecting the androgen deprivation state in prostate cancer bone metastasis

In castrate-resistant prostate cancer (CRPC), the prevailing organ for metastasis is bone, where the survival of cancer cells is regulated by the permissive metastatic niche offered by the bone marrow. The tumour microenvironment and cellular interactions with the matrix and bone cells enable metastasis and lead to cancer cells becoming androgen resistant. Hence, 3D models that mimic CRPC in terms of an androgen deprivation state (ADS) are needed to identify the mechanisms for CPRC growth in bone and further develop therapeutic strategies.

Investigating the role of neuroendocrine transdifferentiation in the progression to castration resistant prostate cancer

Androgen targeted therapies (ATT) are the most commonly used treatments in prostate cancer (PCa).While these therapies are initially effective, PCa cells are able to activate adaptive response pathways to survive these therapies and progress to castration resistant PCa (CRPC), a highly aggressive and ultimately lethal stage of the disease. Neuroendocrine transdifferentiation (NEtD), a process whereby PCa cells gain neuroendocrinelike characteristics, has been implicated in the development of CRPC. The objective of this study is to develop and characterise models of therapy-induced NEtD to investigate the role of this adaptive plasticity in the progression to CRPC.

Targeting neuropilin-1 to inhibit prostate cancer invasion and metastasis

Recent reports provide evidence that the epithelial-to-mesenchymal transition (EMT) plays a key role in prostate cancer (PCa) metastasis and therapy resistance. We have recently identified the cell surface receptor, Neuropilin-1 (NRP1) to be increased during epithelial-mesenchymal transition (EMT) and this study aims to determine whether the inhibition of NRP1 will be a feasible therapeutic strategy for blocking PCa metastasis and therapy resistance.