Research highlights

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. Key trials underpinning this effort include Prostate TRACERx, PEACE and NEPTUNES 

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 mass spectrometry techniques, 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. Bladder cancer has yielded notable successes but the majority of patients still gain limited benefit. This may be in part due to low mutational burdens, low neoepitope presentation or impaired T-cell migration. We are conducting a number of Early Phase Clinical trials of small molecule inhibitors, vaccines, immune checkpoint inhibitors and Bispecific T-cell engagers (BITEs) within the UCLH/NIHR Clinical Research Facility. We are the lead site for the Biontech Prostate Cancer Vaccine study called Pro-MERIT and are exploring peptide vaccines in combination with checkpoint inhibitors in early bladder cancers (DURANCE study). 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 rational therapeutic combinations.