The Translational Research Network for Prostate Cancer (TransPot) program adopts an innovative, multidisciplinary approach, providing highly sought-after, effective solutions for incurable prostate cancer (PC). The TransPot scientific objective is to obtain an unmatched depth of molecular, mechanistic and informatics systems-level disease understanding in order to improve the prognosis and treatment of lethal PC, aimed to (i) provide important insights into molecular mechanisms driving treatment resistant PC including castrate-resistant PC (CRPC), (ii) identify novel therapeutic targets, (iii) develop and validate predictive models for disease progression, prognosis and responsiveness to current and novel (co-)treatment options, and (iv) provide superior, clinically relevant tools and biomarker signatures for personalising and optimising CRPC therapy. Our research program is built on network-wide, state-of-the-art cancer biology-based mechanistic research integrated with a systems medicine approach: 1. Cancer biology-based mechanistic research incorporating a comprehensive range of model systems incorporating unique, pre-clinical and clinical resources and distinct phenotypic high content screen platforms. 2. A systems medicine approach with mathematical modelling to develop novel predictive/prognostic tools. 3. Centres of excellence in surgery, oncology and clinical trials, comprising clinical infrastructure and essential resources whereby candidate therapeutic targets and predictive/prognostic tools can be comprehensively evaluated, including accessing bio-repository resources. We will train young scientists to apply multiple ‘omics’ technologies and approaches in model systems and systems biology to answer important clinically-relevant questions. Advances achieved will facilitate personalized targeted-medicine in treating lethal PC, and will impact beyond the scientific community by improving the well-being of advanced PC patients.