Genomic and Immune Heterogeneity in Prostate Cancer
Prostate cancer is the second most common malignancy in men leading to an estimated 307,000 deaths worldwide. The majority of patients that present with prostate cancer in the western world have prostate confined, low risk disease with a 98.8% 10-year survival. However, the patients that present with high-risk prostate cancer have significant mortality rates despite radical treatments. A key challenge in prostate cancer is being able to identify with certainty patients with high-risk and treat them, while avoiding overtreatment in the low-risk group. The UCBG aims to tackle this by investigating the prostate cancer heterogeneity through high coverage genomic sequencing, proteomics and immune infiltrate analysis. This is taking place through collaborations between the UCBG and the Surgery and Interventional Trials Unit, Translational Cancer Therapeutics, Tumour Immunotherapy Group and the Prostate International Cancer Genomic Consortium.
Signalling Heterogeneity in Prostate Cancer
Even morphologically normal regions of the prostate have been shown to contain possible cancer drivers. When evaluating whether a prostate tumour is potentially lethal, an understanding of the activated oncogenic signalling networks within that region could be key. Using multi-regional TMT-mass spectrometry, array based kinase assays and computational biology we aim to identify activated signalling nodes and test their functional relevance as potential therapeutic targets.
Early Phase Clinical Trials of Targeted Therapy
Immune checkpoint inhibition in prostate cancer has so far been of limited success. This may be in part due to low mutational load, low neoepitope presentation or could be due to impaired T-cell migration into the prostate cancer. We are conducting a number of Early Phase Clinical trials of small molecule inhibitors and immune checkpoint inhibitors within the UCLH/NIHR Clinical Research Facility. Using clinical samples generously donated from patients enrolled in these trials, we are studying the immune landscape to help better understand responses and resistance to these exciting new treatments and to develop rationale therapeutic combinations.