Prostate cancer is the leading type of cancer diagnosed in men. In 2010, ∼217,730 new cases of prostate cancer were reported in the United States. Prompt diagnosis of the disease can substantially improve its clinical outcome. Improving capability for early detection, as well as developing new therapeutic targets in advanced disease are research priorities that will ultimately lead to better patient survival. Eukaryotic cells secrete proteins via distinct regulated mechanisms which are either ER/Golgi dependent or microvesicle mediated. The release of microvesicles has been shown to provide a novel mechanism for intercellular communication. Exosomes are nanometer sized cup-shaped membrane vesicles which are secreted from normal and cancerous cells. They are present in various biological fluids and are rich in characteristic proteins. Exosomes may thus have potential both in facilitating early diagnosis via less invasive procedures or be candidates for novel therapeutic approaches for castration resistance prostate cancer. Because exosomes have been shown previously to have a role in cell-cell communication in the local tumor microenvironment, conferring activation of numerous survival mechanisms, we characterized constitutive lipids, cholesterol and proteins from exosomes derived from six prostate cell lines and tracked their uptake in both cancerous and benign prostate cell lines respectively. Our comprehensive proteomic and lipidomic analysis of prostate derived exosomes could provide insight for future work on both biomarker and therapeutic targets for the treatment of prostate cancer.

Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment

Epidemiological studies indicate that vitamin D insufficiency could have an etiological role in prostate cancer. In addition, calcitriol, used in combination with currently available drugs, has the potential to potentiate their anticancer effects or act synergistically by inhibiting distinct mechanisms involved in prostate cancer growth. Clinical data have not yet provided sufficient evidence to demonstrate benefit of vitamin D due to the limited and underpowered studies that have been published to date. Here, we review the preclinical and clinical studies that describe the activity of calcitriol, applied either alone or in combination and assessed the mechanistic basis of pharmacodynamic and pharmacokinetic interactions with calcitriol. Important considerations for calcitriol use in combination therapy with respect to safety and clinical outcomes have been discussed. Many of these combinations have therapeutic potential for the treatment of several cancer types and it is anticipated that future clinical research will put emphasis on well‑designed clinical trials to establish efficacy.