Andrology-Open Access
Open Access

Abstract

Androgen Receptor and the Fatty Acid-Binding Protein 5 in Malignant Progression of Prostate Cancer and in Development of Resistance to Treatment

Abdulghani A Naeem, Saud A Abdulsamad, Jiacheng Zhang, Wenzhi Guo, Gang He and Youqiang Ke*

Background: Prostate cancer is one the most common cancers of men worldwide and a leading curse of death from male malignant diseases. Androgen Receptor (AR) and Fatty Acid-Binding Protein 5 (FABP5) play important roles in prostate cancer development, expansion, and malignant progression.

Objectives: In this short review, we intend to provide an overview on roles of AR and FABP5 play in development, progression of prostate cancer and the development of resistance to current treatment. We also intend to discuss the possible future effective treatment for Castration-Resistant Prostate Cancer (CRPC) which is currently an incurable disease.

Methods: The literature survey in this study was conducted by searching databases, including EBSCO Host information services, National Library of Medicine, Oxford Academic, Acta Pharmacologica Sinica, Elsevier Database, National Cancer Institute, Harvard Health Publishing, and Memorial Sloan Kettering Cancer Center.

Results and discussion: Androgens or male hormone is essential for normal prostate growth. AR responds to androgen binding, which in turn activates a cascade of conformational changes, that enables androgen to reach prostate cells to initiate transcriptional activity, and to alter the gene expressions. Over-activation of androgen through AR leads to the development of prostate cancer. Drugs developed to control the interactions between androgens and their receptor to inhibit the growth of the cancer cells. However, as the prolonged Androgen-Deprivation Therapy (ADT), the resistance to the treatment is gradually developed: Androgen-dependent prostate cancer gradually become CRPC. The promotive role of androgen-initiated signal pathway was gradually replaced by FABP5-initiated signal transduction pathway, which eventually become dominant in CRPC cells.

Conclusion: For a future effective CRPC treatment, ADT should be combined with inhibition of FABP5. The suppression of both AR and FABP5-expression (including gene knockout) in the cancer cells may provide a new way for an effective treatment of CRPC.

Published Date: 2025-02-20; Received Date: 2024-12-21