Research Interest

Tissue marker studies in patients managed in prospective clinical studies

We have demonstrated the feasibility of evaluating candidate tissue biomarkers using a novel biopsy tissue micro array (TMA) technique developed at the ICR. TMAs have been constructed from 200 patients from the active surveillance study and we will evaluate expression of a range of candidate biomarkers (eg. Ki 67, Bcl2, VEGF, HIF-1alpha, E cadherin, SPINK1) with respect to disease progression.

Biopsy tissue microarray (TMA) construction

Radiotherapy dose-escalation improves disease control, but also increases treatment-related morbidity. Identification of biomarkers that predict for benefit from dose-escalation would be valuable. Proof of principle has been provided by demonstrating that markers related to hypoxia (HIF1, VEGF, osteopontin) were related to outcome both in patients treated by RT (201 patients treated in RMH/ICR dose-escalation study and MRC RT01) as well as an independent set of patients treated by prostatectomy (289 men treated at Aarhus University Hospital).  

We shall assess proliferation related (eg Ki-67, cyclin A), apoptosis (fig) and hypoxia markers in relation to dose-escalation and fraction size sensitivity from patients treated in RT01 (N=850), RMH dose-escalation (N=126), CHHiP (N=3160) and pelvic IMRT (N=320) studies.

Tissue collection and TMA construction are the subject of further grant applications. The studies will ‘stand-alone’ but be part of a planned comprehensive program to construct TMAs from patients with a spectrum of disease and managed in a variety of ways (eg active-surveillance, intermediate, high or very high-risk disease and metastatic disease) included in appropriate ongoing clinical trials in collaboration with the MRC and ICR CTSU.

Benefit of radiotherapy dose-escalation with respect to apoptotic marker expression of BCL-2: Preliminary analysis of data from Dose escalation and RT01 studies.

The goal will be to improve treatment individualisation for patients based on novel combinations of biological markers.