Abstract
CTCs have extensively been used for the monitoring and characterization of metastatic prostate cancer, but their application in the clinic is still very scarce. Besides, the resistance mechanisms linked to prostate cancer treatment remain unclear. Liquid biopsies represent the most promising alternative due to the complexity of biopsying bone metastasis and the duration of the disease. We performed a prospective longitudinal study in CTCs from 20 castration-resistant prostate cancer patients treated with docetaxel. For that, we used CellSearch® technology and a custom gene expression panel with qRT-PCR using a CTCs negative enrichment approach. We found that CTCs showed a hybrid phenotype during the disease, where epithelial features were associated with the presence of ≥ 5 CTCs/7.5 mL of blood, while high relative expression of the gene MYCL was observed preferentially in the set of samples with < 5 CTCs/7.5 mL of blood. At baseline, patients whose CTCs had stem or hybrid features showed a later progression. After 1 cycle of docetaxel, high relative expression of ZEB1 indicated worse outcome, while KRT19 and KLK3 high expression could predisposed the patients to a worse prognosis at clinical progression. In the present work we describe biomarkers with clinical relevance for the prediction of early response or resistance in castration-resistant prostate cancer patients. Besides, we question the utility of targeted isolated CTCs and the use of a limited number of markers to define the CTCs population.
Highlights
Prostate cancer (PC) is the fifth leading cause of cancerrelated death worldwide and the second most commonly diagnosed cancer in men [1]
The mechanisms involved in this process are still unclear, it has been reported that continued signalling of androgen receptors (AR) is critical to the development of castration-resistant PC (CRPC) [3]
The Cellsearch is an EpCAM-based system that only considers those CTCs with epithelial features (Figure S1)
Summary
Prostate cancer (PC) is the fifth leading cause of cancerrelated death worldwide and the second most commonly diagnosed cancer in men [1]. Detection and new advances in PC treatment are improving the survival rate and the quality of life of diagnosed patients; the prediction for the upcoming years is of 379,000 deaths worldwide in 2040 [1]. Androgen deprivation therapy (ADT) is the first-line treatment of choice for men with advanced PC. The mechanisms involved in this process are still unclear, it has been reported that continued signalling of androgen receptors (AR) is critical to the development of CRPC [3]. For advanced CRPC, taxanes, new anti-androgen inhibitors or Radium223 are active agents, but the development of biomarkers it is still needed to select the most effective and less toxic treatment for each patient [4]
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