We have initiated 10-15 studies each year since the beginning of ECMC funding, including 6 in which Cancer Research UK has a major investment. The most advanced of these in development is abiraterone, which is predicted to make a major impact in the treatment of castration resistant prostate cancer. The number of patients entering trials per year has increased each year; 293 patients entered Phase I trials in the past 12 months, and at any one time approximately 30 trials are open to recruitment.

Building on our earlier work last year, we have set up a unique European collaboration, involving all the major Phase I centres, in order to establish an accepted formula for measuring/predicting prognosis of patients referred for Phase I trials. The database now comprises more than 1500 cases, and includes information from 4 ECMC sites.

A molecular pathology facility has been established with tumour sequencing equipment funded by ECMC utilizing mass spectroscopy based sequencing. We are now routinely collecting archival tumour tissue from all patients at the time of initial referral to the Drug Development Unit and are pursuing tumour molecular characterization studies by FISH, immunohistochemistry (PTEN) and microdissected tumour cell sequencing of kinases of interest such as PI3KC p110α. We are concurrently comparing circulating tumour cell and tumour biopsy molecular data and about 15% of patients now undergo tumour biopsies.

We have continued to optimize functional imaging protocols to establish robust non-invasive biomarkers for clinical trials.

Over the past 12 months we have taken 4 compounds which originated in the CRUK Centre for Cancer Therapeutics through to Phase I clinical trials in the Drug Development Unit; these are: the non-geldanamycin HSP90 inhibitor (with Novartis), the PI3K inhibitor (with Genentech), the α-folate receptor targeted TS inhibitor (Onyx) and the HDAC inhibitor (with Chroma). In addition we have initiated the first trials with the ICR drug, abiraterone, in breast cancer (with Johnson & Johnson).

We have provided the first definitive evidence of PARP inhibitor response in BRCA associated cancer, and demonstrated a clear correlation with prior platinum response. The overall response rate was 50% with an excellent toxicity profile. These data were derived from a series of 50 patients with BRCA-associated ovarian cancer treated with olaparib and directly led to 2 international randomized trials. In addition we have preliminary evidence of efficacy in selected patients with sporadic ovarian cancer, and are now working with 2 other PARP inhibitors.

We have demonstrated proof of principle for the PI3K inhibitor by showing inhibition of AKT phosphorylation and its downstream signaling in platelet rich plasma and serial tumour biopsies taken from patients in the first in man Phase I trial. We have utilized these assays in the evaluation of a first in man, first in class, AKT inhibitor and have also developed hair follicle assays of AKT pathway signaling, demonstrating p-PRAS40 knockdown following treatment.

We have continued to assess the potential of circulating tumour cells (CTC) for predictive, intermediate endpoint and pharmacodynamic biomarkers; we are currently evaluating three different CTC technology platforms for their separation from other plasma components. We have shown the prognostic relevance of CTC fragments and have been closely involved in drawing up new definitions for what comprises a CTC.