What is the Origin of Intratumoral Androgen Synthesis?

This concept emerged from clinical observations that prostate cancer often progresses despite achieving castrate levels of circulating testosterone. Molecular endocrinology research subsequently identified the necessary enzymatic machinery within the tumor cells themselves. The term highlights the autonomous nature of hormone production within the pathological tissue.

What is the Mechanism of Intratumoral Androgen Synthesis?

The primary mechanism involves the upregulation of key steroidogenic enzymes within the tumor cell, including CYP17A1, 3β-hydroxysteroid dehydrogenase, and 17β-hydroxysteroid dehydrogenase. These enzymes convert circulating adrenal androgens, such as DHEA and androstenedione, into potent androgens like DHT, which then bind to the androgen receptor to promote cell survival and proliferation. This localized production ensures continuous, autocrine stimulation of the cancer cells, rendering systemic ADT less effective over time.

Intratumoral Androgen Synthesis ∞ Area

Intratumoral Androgen Synthesis

Meaning

Intratumoral androgen synthesis refers to the biochemical process where cancer cells, specifically within the tumor microenvironment, acquire the ability to synthesize androgens, such as testosterone and dihydrotestosterone (DHT), de novo from adrenal precursors or cholesterol. This localized synthesis pathway allows the tumor to bypass the effects of systemic androgen deprivation therapy (ADT), which primarily targets testicular androgen production. This mechanism is a critical driver of castration-resistant prostate cancer progression. Understanding and targeting the enzymes involved in this local steroidogenesis is a major focus in oncology research.