Personalised Medicine: The UK Experience

Abstract

'Personalised medicine' means tailoring cancer treatment very precisely to an individual person's cancer. Somatic mutation testing in patients with solid tumours is already happening and demand is predicted to increase, but published data suggest there are issues with the reproducibility and accuracy of results; for widespread use, techniques should preferably work in formalin-fixed, paraffin embedded tissue. Cancer Research UK set up a national programme, Stratified Medicine Programme (SMP) to test whether this was possible and to provide the foundations for a future national service. Phase I of the SMP was conducted in 8 Experimental Cancer Medicine Centres (ECMCS) across the UK, between September and June 2013. The aim was to collect and analyse up to 9,000 tumour and corresponding blood samples from breast (PIK3CA, TP53, BRAF, PTEN mutation and PTEN LOH by microsatellite analysis), prostate (PTEN and BRAF mutation, TMPRSS2-ERG fusion by FISH BUT moving to rt-PCR, and PTEN LOH by microsatellite analysis), lung (EGFR, KRAS, BRAF mutation and ALK rearrangement by FISH), ovary (TP53, PTEN, PIK3CA and BRAF mutation and PTEN LOH by microsatellite analysis) and colorectal (KRAS, BRAF, NRAS, PIK3CA, TP53) cancer and melanoma (PTEN and BRAF mutation, TMPRSS2-ERG fusion by FISH but moving to rt-PCR, and PTEN LOH by microsatellite analysis) to be sent from the Clinical Hubs to Technology Hubs for testing; the results were then to be fed back to the Clinical Hubs. In Leeds we planned to collect tumour/blood samples from patients with breast cancer (350 patients), ovarian cancer (250), colorectal cancer (150) and melanoma (150). Internal processes were set up to collect all these samples in collaboration with the corresponding clinical, medical, pathology and phlebotomy/clinical biochemistry teams and where possible in alignment with routine clinical practice or existing research needs; these tissues samples were sent to the Royal Marsden Technology Hub for analysis. The mutational analysis results were then returned to the Clinical Hubs and linked to an electronic patient information data set. The national programme was completed successfully. We are now setting up Phase II, focussing on patients with lung cancer with a view to their inclusion in trials of novel targeted agents.