: Exosomes are nano-membrane vesicles that various cell types secrete during physiological
and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins,
and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including
cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate
cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move
into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis.
Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a
tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCaderived exosomes and the TME remains only partially understood. In this review, we provide new
insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming
the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the
molecular mechanisms of TME reprogramming by exosomes draws more practical and universal
conclusions for the development of new therapeutic interventions when considering TME in the
treatment of PCa patients.