The role of adrenal derived androgens in castration resistant prostate cancer
| Autor: | Karl-Heinz Storbeck, Monique Barnard, Elahe A. Mostaghel, Richard J. Auchus |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Androgen biosynthesis Male medicine.drug_class Endocrinology Diabetes and Metabolism Clinical Biochemistry Context (language use) Castration resistant urologic and male genital diseases Biochemistry Article Androgen deprivation therapy 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine Endocrinology medicine Humans Molecular Biology Testosterone business.industry Androgen Antagonists Cell Biology Androgen medicine.disease Prostatic Neoplasms Castration-Resistant 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research Androgens Molecular Medicine 11-Ketotestosterone business |
| Zdroj: | J Steroid Biochem Mol Biol |
| ISSN: | 1879-1220 |
| Popis: | Castration resistant prostate cancer (CRPC) remains androgen dependant despite castrate levels of circulating testosterone following androgen deprivation therapy, the first line of treatment for advanced metstatic prostate cancer. CRPC is characterized by alterations in the expression levels of steroidgenic enzymes that enable the tumour to derive potent androgens from circulating adrenal androgen precursors. Intratumoral androgen biosynthesis leads to the localized production of both canonical androgens such as 5α-dihydrotestosterone (DHT) as well as less well characterized 11-oxygenated androgens, which until recently have been overlooked in the context of CRPC. In this review we discuss the contribution of both canonical and 11-oxygenated androgen precursors to the intratumoral androgen pool in CRPC. We present evidence that CRPC remains androgen dependent and discuss the alterations in steroidogenic enzyme expression and how these affect the various pathways to intratumoral androgen biosynthesis. Finally we summarize the current treatment strategies for targeting adrenal derived androgen biosynthesis. |
| Databáze: | OpenAIRE |
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