Related Experiment Video

Updated: Jan 16, 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

11.7K

The future of androgen receptor targeting in prostate cancer: third-generation inhibitors and beyond

Alice Bernard-Tessier1,2, Natacha Naoun1, Solenn Barraud1

  • 1Department of Cancer Medicine, Gustave Roussy, Villejuif, France, Paris-Saclay University, Kremlin-Bicetre, France.

Therapeutic Advances in Medical Oncology
|October 2, 2025
PubMed

Insights

Emerging resistance to androgen receptor pathway inhibitors (ARPI) in prostate cancer necessitates new treatments. This review explores resistance mechanisms and highlights advanced therapies like CYP11A1 inhibitors and AR degraders for improved patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The androgen receptor (AR) pathway is critical in prostate cancer treatment, including castration-resistant prostate cancer (CRPC).
  • Second-generation AR pathway inhibitors (ARPI) offer benefits, but treatment resistance remains a significant clinical challenge.
  • Understanding ARPI resistance mechanisms is vital for developing novel therapeutic strategies.

Purpose of the Study:

  • To review the biological mechanisms underlying resistance to second-generation ARPI in prostate cancer.
  • To discuss emerging third-generation ARPI and steroid hormone inhibitors.
  • To highlight novel therapeutic targets and biomarkers for personalized prostate cancer treatment.

Main Methods:

  • Literature review of current research on ARPI resistance in prostate cancer.
  • Analysis of emerging therapeutic strategies targeting AR pathway.
  • Discussion of potential biomarkers for patient stratification.

Main Results:

  • Resistance to ARPI is a complex biological process requiring further investigation.
  • Advanced therapeutic strategies include CYP11A1 inhibition, proteolysis-targeting chimera degraders, and EZH2 inhibitors.
  • AR genomic alterations, particularly mutations, show promise as predictive biomarkers.

Conclusions:

  • Developing novel therapeutics targeting ARPI resistance is crucial for improving outcomes in advanced prostate cancer.
  • Third-generation ARPI, steroid hormone inhibitors, and targeted degradation offer promising avenues.
  • Personalized treatment approaches incorporating biomarkers like AR mutations will enhance patient care.
Keywords:
AR alterationsAR-targeted therapyandrogen receptor pathway inhibitorcastration-resistant prostate cancerdrug resistance

More Related Videos

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.7K
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

11.1K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.7K
Adrenergic Antagonists: ɑ and β-Receptor Blockers01:31

Adrenergic Antagonists: ɑ and β-Receptor Blockers

Third-generation β-blockers, such as labetalol and carvedilol, represent a significant advancement in managing cardiovascular conditions. Unlike conventional β-blockers, which can induce peripheral vasoconstriction, third-generation drugs block α1 adrenoceptors. This promotes vasodilation through several mechanisms, such as increased nitric oxide production, inhibition of calcium ion entry, opening of potassium ion channels, and antioxidant action. Labetalol, for instance, is...
1.1K
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...
462
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
10.0K