Targeted nanomedicine modalities for prostate cancer treatment

Abstract

Prostate cancer (PC) is the second most common cause of death amongst men in the USA. Therapy of PC has been transformed in the past decade by introducing novel therapeutics, advanced functional imaging and diagnostic approaches, next generation sequencing, as well as improved application of existing therapies in localized PC. Treatment of PC at the different stages of the disease may include surgery, androgen deprivation therapy (ADT), chemotherapy and radiation therapy. However, although ADT has proven efficacious in PC treatment, its effectiveness may be temporary, as these tumors frequently develop molecular mechanisms of therapy resistance, which allow them to survive and proliferate even under conditions of testosterone deprivation, inhibition of androgen receptor signaling, or cytotoxic drug treatment. Importantly, ADT was found to induce key alterations which frequently result in the formation of metastatic tumors displaying a therapy refractory phenotype. Hence, to overcome these serious therapeutic impediments, novel PC cell-targeted therapeutic strategies are being developed. These include diverse platforms enabling specific enhanced antitumor drug uptake and increased intracellular accumulation. Studies have shown that these novel treatment modalities lead to enhanced antitumor activity and diminished systemic toxicity due to the use of selective targeting and decreased drug doses. The underlying mechanism of targeting and internalization is based upon the interaction between a selective ligand, conjugated to a drug-loaded nanoparticle or directly to an anti-cancer drug, and a specific plasma membrane biomarker, uniquely overexpressed on the surface of PC cells. Another targeted therapeutic approach is the delivery of unique anti-oncogenic signaling pathway-based therapeutic drugs, which are selectively cytotoxic to PC cells. The current paper reviews PC targeted modalities reported in the past 6 years, and discusses both the advantages and limitations of the various targeted treatment strategies.

Keywords: Androgen deprivation therapy; Anti-androgens; Castration-resistant prostate cancer; Chemotherapy; Drug-ligand conjugate; Nanoparticles; Oncogenic pathways; Phytochemicals; Prostate cancer; Targeted therapeutics.