Recent discoveries in the biology of prostate cancer have enabled scientists to develop drugs targeting specific molecules that promote tumor growth or make the tumor resistant to treatment. However, while these agents, such as Zytiga (abiraterone acetate) and enzalutamide (MDV3100), have provided dramatic benefit for many patients, not all respond, and among those who do, the durability of response can be limited. Biomarker assays -- tests that can provide information on the biologic profile of an individual patient's tumor -- have the potential to revolutionize the management of prostate cancer by (1) helping identify which treatments are most likely to benefit which individual patients, (2) reducing the chance of exposing patients to ineffective, costly, and potentially toxic treatments, and (3) accelerating the drug development process by enabling clinical trials to enroll patients most likely to respond to the treatment being studied.

Analytical validation is a rigorous process used to establish the performance characteristics of the biomarker assay itself, including the method, reagents, and device(s) used, and the range of conditions under which the measurement gives reproducible and accurate results. Only validated assays for biomarkers can be used to guide treatment selection. Critically, however, there are currently no validated assays to measure key predictive prostate cancer biomarkers.

The overarching goal of our Multicenter Assay Validation Program is to synchronize the many different elements currently involved in biomarker development in order to make analytically valid assays (i.e., biomarker tests) available in the near-term. As a result, the drugs that are most likely to benefit individual patients can be used and the patients will be spared the side effects from ineffective therapies.

To meet our objective, we have assembled a uniquely qualified team of multidisciplinary investigators from five premier academic medical centers and industry to validate biomarker assays across multiple institutions, defining how the tests must be conducted to ensure that valid results will be produced. We have selected an initial set of five assays for biomarkers corresponding to the two most frequently altered molecular pathways in human prostate cancer -- the androgen receptor (AR) and PI3K pathways. These pathways are especially attractive drug targets, as we have discovered that inhibiting the PI3K pathway overcomes the resistance that some prostate tumors have (or develop in response to treatment) to AR inhibition. For these reasons, multiple clinical trials of drugs targeting these pathways, alone or in combination, are currently under way or will soon begin, and the need for validated assays showing which patients are most likely to respond to which drugs is paramount.

During the second phase of our program we will begin multicenter validation of five additional candidate biomarkers, particularly those that are being identified by gene sequencing projects such as the Stand Up To Cancer - Prostate Cancer Foundation Prostate Dream Team Translational Cancer Research Grant. To address the challenges of validating next-generation molecular assays, we will utilize the specific expertise of our Bioinformatics Co-Leaders to process and analyze the data these projects will produce, to develop ad hoc software and database solutions, and to perform computer simulations.

By creating the only mechanism with the ability to bring together leaders in the fields of prostate cancer pathology, medical oncology, computational biology, and statistics to specifically address assay validation, we intend to bring about an era of precision medicine where the choice of treatment is based on the real-time biologic profile of an individual patient's tumor.