A43
Analysis of circulating tumour cells in prostate cancer patients for predictors of therapeutic response and prognosis
Jeremy Clark1, Christophe Massard1, Geraldine Perkins1, Juliet Dukes1, Mateus Crespo1, Fyllitsa Ntouroupi3, Joana Moreira2, David Olmos1, Walter Bodmer3, Colin Cooper1, Johann De Bono2
1ICR, Sutton, UK, 2RMHNHS Trust, Sutton, UK, 3Weatherall Institute, Oxford, UK
Prostate cancer is the most common male cancer in the US. It is a polymorphic disease and progression is highly variable resulting in mortality in ~10% of patients. Circulating tumour cell (CTC) numbers have been shown to be prognostic indicating that CTCs can reflect disease status. We are further investigating the potential for CTCs to be used as a liquid biopsy for assessment of therapeutic response and mechanisms of resistance. This information could then be used to alter the therapeutic regime on an individual basis.
We are developing a rapid method of harvesting CTCs that allows gene copy number, translocation and mutation analysis of CTCs from a single blood sample. It also enables us to extract circulating DNA and RNA from plasma from the same sample for tumour mutation analysis. The filtration method relies on the principle that CTCs are larger than normal blood cells and can thus be separated from them by size filtration. Duplicate blood samples will be used to make direct comparisons between CTC counts with the filtration system and those obtained by the Veridex CTC counting system. Preliminary data has demonstrated that FISH assessment of TMPRSS2/ERG translocation status and androgen receptor (AR) copy number on filtered patient CTCs is readily achievable. AR mutations have been detected by sequencing or RT-PCR products obtained from filtered bloods seeded with ~10 LNCaP cells. We have currently filtered >100 patient samples from a range of drug studies including Abiraterone and will further process these samples for CTC counts, FISH and mutation analysis for information on the therapeutic efficacy and patient prognosis.
