Abstract
There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management.
Highlights
Background and Focus of This PerspectivePublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Licensee MDPI, Basel, Switzerland.Prostate cancer (PCa) was the second most frequently diagnosed cancer and the second and fifth leading cause of cancer death among Canadian men and men worldwide, respectively, in 2020 [1]
The focus of this article is on the underappreciated potential of targeting cholesterol metabolism in the advanced disease state and how understanding the role of scavenger receptor class B member 1 (SR-B1) may reveal potential therapeutic opportunities related to cholesterol ester (CE) uptake for de novo steroidogenesis and cellular homeostasis
Androgen receptor (AR) activity is the primary driver of PCa, and its activation persists in the vast majority of castration-resistant prostate cancer (CRPC), in part, due to intratumoral androgen synthesis [8,9,10,11]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Androgen deprivation therapy (ADT) is effective for treating PCas that fail primary curative-intent therapies; remission is temporary [2,3], and disease re-emergence or castration-resistant prostate cancer (CRPC) occurs in approximately. Reviewed [7] advances in the understanding of the disease landscape and the mechanisms of progression have resulted in a remarkable array of therapies that have greatly increased the survival of patients with incurable metastatic disease. The focus of this article is on the underappreciated potential of targeting cholesterol metabolism in the advanced disease state and how understanding the role of scavenger receptor class B member 1 (SR-B1) may reveal potential therapeutic opportunities related to cholesterol ester (CE) uptake for de novo steroidogenesis and cellular homeostasis.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
