Grant: Travel Awards - Institute Community Support

Late-stage prostate cancer (PCa) is invariably lethal. Despite many available treatment options, there are few biomarkers to assist with pairing drugs to individual patients who are most likely to receive benefit. This means that many patients are ultimately treated with drugs that are ineffective for their individual cancer, leading to unnecessary toxicity and wasted time as their disease worsens. Herein lies an urgent clinical need for tests that can identify patients most likely to respond to therapy, thereby helping clinicians select the best cancer treatment for an individual patient. A minority of PCas harbour rare mutations (in genes AKT1 or PIK3CA) that may predict favourable response to the drug Ipatisertib. Our aim was to develop a test to identify these patients who may benefit, and furthermore understand the molecular and clinical features of this rare subtype. 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 tumor 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. We have obtained blood samples from 774 patients with advanced PCa. The DNA extracted from these blood samples was profiled to identify patients whose cancer harboured AKT1 or PIK3CA mutations. These mutations were identified in 5.8% of patients and were associated with aggressive molecular features. My work suggests that ctDNA profiling can identify patients with AKT1 / PIK3CA mutations who may respond to novel targeted therapy. Work is ongoing to understand the clinical features of these patients, including their response to standard-of-care drugs.