Grant: Doctoral Research Award: Canada Graduate Scholarships

The primary chemotherapy for late-stage prostate cancer is only effective in 45% of patients. However, there is currently no way of knowing in advance which patients will benefit from treatment, and which patients could avoid the side-effects of chemotherapy through receiving a different therapy instead. Herein lies an urgent clinical need for tests that can predict patient response to chemotherapy, thereby helping clinicians select the best cancer treatment for an individual patient. Our aim is to identify molecular markers capable of predicting whether a patient will respond to the chemotherapy docetaxel. Our assay relies on the fact that cancerous tissues shed a small amount of their DNA into the bloodstream, creating an opportunity to examine the tumour by analyzing DNA isolated from a patient's blood sample. This DNA, termed 'circulating tumor DNA' (ctDNA), provides a molecular snapshot of the tumor. CtDNA profiling is a novel technique that enables us to extract information about a cancer via a routine blood test, where it can be quickly translated to the clinic to inform treatment decisions, eliminating the need for invasive tissue biopsies. Over the next three years we will have obtained blood samples from 216 patients with advanced prostate cancer beginning treatment with docetaxel chemotherapy. In this project we will extract the ctDNA from the blood samples, and perform DNA sequencing to detect changes present in each patient's cancer. We can correlate the DNA changes that we find with the patient's clinical outcome, and find the changes that would have predicted how the patient responded to treatment. Finally we will confirm that our predictive 'biomarkers' indeed work, by testing them in blood samples collected from an independent cohort of patients receiving chemotherapy at our cancer centre. This will help us understand why some cancers are resistant, and we will have developed a test to help select the best treatment for an individual patient.