Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer.

The use of circulating tumor cells (CTCs) and circulating extracellular vesicles (EVs), such as exosomes, as liquid biopsy-derived biomarkers for cancers have been investigated. CTC enumeration using the CellSearch based platform provides an accurate insight on overall survival where higher CTC counts indicate poor prognosis for patients with advanced metastatic cancer. EVs provide information based on their lipid, protein, and nucleic acid content and can be isolated from biofluids and analyzed from a relatively small volume, providing a routine and non-invasive modality to monitor disease progression. Our pilot experiment by assessing the level of two subpopulations of small EVs, the CD9 positive and CD63 positive EVs, showed that the CD9 positive EV level is higher in plasma from patients with advanced metastatic prostate cancer with detectable CTCs. These data show the potential utility of a particular EV subpopulation to serve as biomarkers for advanced metastatic prostate cancer. EVs can potentially be utilized as biomarkers to provide accurate genotypic and phenotypic information for advanced prostate cancer, where new strategies to design a more personalized therapy is currently the focus of considerable investigation.

A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer.

OBJECTIVE: Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT. METHOD: A 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL. RESULTS: 42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) vs -0.7 (-1.5 to 0.2) nmol/L; P < 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ -0.4 (-0.9 to -0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (-0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g; P < 0.02] and lean mass [∆ 0.8 (-0.1 to 1.7) kg; P = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels. CONCLUSION: LTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women.