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Prostate cancer exosomes as molecular predictors of response to therapy
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Prostate cancer is the second most common cancer in men and acording to the Globocan report from
2012, there will be over 1.2 million new cases and over 300 000 deaths, worldwide. Organ-defined
prostate cancer is a curable disease, but then it develops into metastatic castration resistant prostate
cancer, and it is usually a matter of time until the patient develops resistance to chemotherapy and
becomes an incurable disease.
This evokes the need for biomarkers that can predict disease progression and response to therapy. This
would allow for a better stratification of the patients to receive the most efficacious, therapeutic
treatment. Cancer cell derived exosomes, with their molecular cargo that represents the tumor cells,
have been demonstrated to be a good source of such prognostic and predictive biomarkers. In this
study we isolated and characterized exosomes derived from prostate cancer cells that are resistant to
docetaxel and abiraterone acetate. One interesting finding is that the cells that are resistant to these two
drugs secrete more exosomes than their sensitive counterparts. We compared the proteomic profile of
these exosomes with exosomes from the parental, drug-sensitive cell lines. We have identified a
number of putative markers that may constitute a predictive signature and are currently under
validation. From our pilot studies we have identified that p-gp positive exosomes may function as
predictive biomarkers for response to docetaxel, and that exosomes containing the splice variant 7 of
the androgen receptor may have the potential to predict response to abiraterone acetate and
enzalutamide. However, both of these biomarkers have to be validated in larger patient cohorts along
with the newly identified proteins. In addition to proteomics, the exosomes are currently being
analysed by transcriptomics, mRNA and miRNA arrays. These combined molecular data will provide
valuable information in finding predictive signatures for response to therapy, in order to provide the
patients with a more personalized medical care and stratified course of treatment, leading to improved
overall survival.
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Palavras-chave
Exosomes mCRPC Biomarkers Resistance Docetaxel Abiraterone acetate