Targeting prostate adenocarcinoma tumor microenvironment via cancer nanotheranostics: a comprehensive update on improved roadmap for disease diagnosis, therapy and management.

Prostate adenocarcinoma (PAC) ranks second as most lethal malignancy in men worldwide with significant economic burden on public health management. Despite of cytoreductive surgery of visible tumor mass followed by administration of chemotherapies including androgen deprivation therapy (ADT) using several drugs including enzalutamide, patients develop therapy resistance displaying metastatic, castration-resistant PAC (mCRPC). Furthermore, mCRPC patients fail to respond to neoadjuvant chemotherapies (NACT) such as androgen receptor-targeted agents (ARTAs) and develop a lethal, highly aggressive, therapy-induced neuroendocrine PAC (NEPC). Hence, identification of novel, targetable drivers and therapeutic interventions are highly warranted to manage this lethal pathology. Recently, nanotheranostics, an approach combining cancer diagnostics and therapeutics via nanotechnology is emerging as a promising intervention strategy towards early detection, disease remission and improved PAC patient survival outcomes. It frequently targets interacting components between cancer cells and tumor microenvironment (TME) which play critical role in disease progression and chemoresistance. For example, multimodal peptide-based imaging probes (peptides complexed with Cu64 etc.) combined with PET-MRI improved early PAC detection and patient survival. In this review, we have comprehensively discussed recent developments in cancer nanotheranostics-their targets in PAC TME, mode of actions and potential therapeutic strategies.