39IN - Will circulating biomarkers help to deliver precision medicine?

Date 27 September 2014
Event ESMO 2014
Session Precision medicine in prostate cancer
Topics Prostate Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter David Olmos Hidalgo
Citation Annals of Oncology (2014) 25 (suppl_4): iv15-iv16. 10.1093/annonc/mdu298
Authors D. Olmos Hidalgo
  • Clinical Research Programme, CNIO- Spanish National Cancer Center, 28029 - Madrid/ES




Precision or personalised medicine represent an emerging approach in treating prostate cancer (PrCa) through the application of available technologies to identify molecular alterations that will allow us to tailor treatments to each particular case. Nonetheless, a preliminary critical step for the application of personalised medicine is to validate this approach through clinical trials that aim either to validate a predictive biomarker of response in a non–‐selected population or to treat a selected population based on a strong biological rationale. A key handicap limiting the general implementation of this approach is the need of available tumour tissue. Since the clonal or polyclonal origin of metastatic disease remains controversial, repeated biopsies may be required as the disease advances.

This difficulty in acquiring tumour tissue has prompted many efforts to identify and validate blood—based circulating biomarkers. Such markers are repeatable, less invasive, and could be easily implemented in clinical practice. The isolation of circulating tumour cells (CTCs)is a good example with a potential utility in delivering precision medicine. CTCs are a surrogate of tumour tissue and have already been employed to identify the expression of targets (i.e. IGF—1R, HER2), tumour mutations (i.e. AR) and genomic events (i.e. AR amplification,TMPRSS2-ERG). Recently, the identification of the alternative splicing variant AR-V7 from CTCs has been suggested as a marker of resistance to enzalutamide or abiraterone and its implementation on clinical trials to stratify patients for these therapies is underway. Genomic wide association studies (GWAS) have previously been used to study PrCa risk, but nowadays are being applied to identify genetic common variants associated with outcomes, treatment response and toxicities. Furthermore, whole blood expression profiling has also proven to be able to stratify advanced PrCa and may hold some potential in selecting patients for immunotherapy. Lastly, the isolation of tumour exosomes as well as circulating— free (cf)—DNA may provide another priceless source tumour material. Current technologies allow to identify genetic/genomic aberrations from cf—DNA, representative of different tumour clones.


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