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Will Circulating Biomarkers Help to Deliver Precision Medicine?
Annals of Oncology 25 (Supplement 4): iv15–iv16, 2014 doi:10.1093/annonc/mdu298.3
special symposium: precision medicine in prostate cancer 39IN
D. Olmos1,2, E. Castro1,2, N. Romero1,2, D. Morales-Pancorbo3 1 Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, SPAIN 2 Centro Integral Oncológico Clara Campal (CIOCC), Madrid, SPAIN 3 Hospital Universitario Virgen De Valme, Seville, SPAIN
abstracts
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
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv15/2240800 by guest on 24 October 2019
WILL CIRCULATING BIOMARKERS HELP TO DELIVER PRECISION MEDICINE?
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. Disclosure: waiting disclosure from speaker.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
special symposium: precision medicine in prostate cancer 39IN
D. Olmos1,2, E. Castro1,2, N. Romero1,2, D. Morales-Pancorbo3 1 Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, SPAIN 2 Centro Integral Oncológico Clara Campal (CIOCC), Madrid, SPAIN 3 Hospital Universitario Virgen De Valme, Seville, SPAIN
abstracts
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
Downloaded from https://academic.oup.com/annonc/article-abstract/25/suppl_4/iv15/2240800 by guest on 24 October 2019
WILL CIRCULATING BIOMARKERS HELP TO DELIVER PRECISION MEDICINE?
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. Disclosure: waiting disclosure from speaker.
© European Society for Medical Oncology 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].