Related Experiment Video

Updated: May 31, 2026

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
08:36

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses

Published on: October 24, 2019

Potential prostate cancer drug target: bioactivation of androstanediol by conversion to dihydrotestosterone

James L Mohler1, Mark A Titus, Elizabeth M Wilson

  • 1Department of Urology, Roswell Park Cancer Institute, Department of Urology, University at Buffalo, State University of New York, Buffalo, New York, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 28, 2011
PubMed

Insights

Dihydrotestosterone (DHT) fuels prostate cancer growth via the backdoor pathway, even during androgen deprivation therapy. Targeting this pathway offers new treatment strategies for advanced prostate cancer.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Dihydrotestosterone (DHT) binding to the androgen receptor (AR) drives androgen-dependent gene activation, crucial for male development and implicated in prostate cancer.
  • Testosterone is the primary circulating androgen, typically converted to DHT by 5α-reductase.
  • Intratumoral androgen production sustains AR activation and prostate cancer growth during androgen deprivation therapy, despite low systemic testosterone.

Purpose of the Study:

  • To elucidate the role of the backdoor pathway in intratumoral DHT synthesis.
  • To identify novel therapeutic targets for enhancing prostate cancer treatment response.

Main Methods:

  • Investigated the metabolism of 5α-androstane-3α, 17β-diol by 17β-hydroxysteroid dehydrogenase 6 in prostate cells.
  • Analyzed the contribution of this pathway to intratumoral DHT synthesis.
  • Evaluated potential drug targets within the backdoor pathway.

Main Results:

  • The metabolism of 5α-androstane-3α, 17β-diol by 17β-hydroxysteroid dehydrogenase 6 is a significant route for intratumoral DHT synthesis.
  • This DHT activates the AR, promoting prostate cancer growth during androgen deprivation therapy.
  • Targeting the backdoor pathway presents a promising strategy to improve therapies.

Conclusions:

  • The backdoor pathway is a critical source of DHT in prostate cancer, contributing to treatment resistance.
  • Inhibiting enzymes in this pathway could enhance the efficacy of current prostate cancer treatments, including LHRH agonists/antagonists and AR antagonists.

More Related Videos

Murine Prostate Micro-dissection and Surgical Castration08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Related Concept Videos

Prodrugs01:30

Prodrugs

Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...
Drug Biotransformation: Overview01:16

Drug Biotransformation: Overview

Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists01:23

Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists

Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...