Signaling Pathways and Targeted Therapies for Stem Cells in Prostate Cancer

Abstract

Prostate cancer (PCa) is one of the most frequently occurring cancers among men, and the current statistics show that it is the second leading cause of cancer-related deaths among men. Over the years, research in PCa treatment and therapies has made many advances. Despite these efforts, the standardized therapies such as radiation, chemotherapy, hormonal therapy and surgery are not considered completely effective in treating advanced and metastatic PCa. In most situations, fast-dividing tumor cells are targeted, leaving behind relatively slowly dividing, chemoresistant cells known as cancer stem cells. Therefore, following the seemingly successful treatments, the lingering quiescent cancer stem cells are able to renew themselves, undergo differentiation into mature tumor cells, and sufficiently reinitiate the disease, leading to cancer relapse. Thus, prostate cancer stem cells (PCSCs) have been reported to play a vital role in controlling the dynamics of tumorigenesis, progression, and resistance to therapies in PCa. However, the complete knowledge on the mechanisms regulating the stemness of PCSCs is still unclear. Thus, studying the stemness of PCSCs will allow for the development of more effective cancer therapies due to the durable response, resulting in a reduction in recurrences of cancer. In this Review, we will specifically describe the molecular mechanisms responsible for regulating the stemness of PCSCs. Furthermore, current developments in stem cell-specific therapeutic approaches along with future prospects will also be discussed.

Figure 1

(a) Primary CRPC with a heterogeneous population of PCa cells treated via androgen deprivation therapy (ADT). (b) While AR⁺ PCa cells were eliminated in ADT, AR^– PCa cells, PCSCs, and a few mutated AR⁺ PCa cells survived the therapy. The depletion of AR leads to overexpression of the ANXA1 gene that encodes annexin A1. (c) Increased annexin A1 accelerates PCa metastasis and invasion.

Figure 2

Illustration of the role of a few miRNAs implicated in PCa.