Related Experiment Video

Updated: Oct 13, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

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

Published on: March 6, 2018

13.3K

Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies

Aasems Jacob1, Rishi Raj2, Derek B Allison3,4,5

  • 1Department of Medicine, Division of Hematology & Oncology, Pikeville Medical Center, Pikeville, KY 41501, USA.

Cancers
|November 13, 2021
PubMed

Insights

Prostate cancer therapies targeting androgen receptor (AR) show promise but resistance develops. Understanding AR-dependent and independent resistance mechanisms is crucial for developing new treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Prostate cancer treatment often involves targeting the androgen receptor (AR) signaling pathway.
  • Androgen-receptor signaling inhibitors (ARSIs) like abiraterone, enzalutamide, apalutamide, and darolutamide have improved survival.
  • However, drug resistance invariably develops, limiting long-term efficacy.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying resistance to ARSIs in prostate cancer.
  • To identify both androgen-dependent and androgen-independent pathways that mediate treatment failure.
  • To inform the development of novel therapeutic strategies to overcome resistance.

Main Methods:

  • Review of current literature on prostate cancer molecular mechanisms and therapeutic resistance.
  • Analysis of known AR-dependent resistance pathways, including AR splice variants (e.g., AR-V7), overexpression, and mutations.
  • Investigation of non-AR-dependent resistance mechanisms involving alternative signaling pathways.

Main Results:

  • Resistance can occur through AR-dependent mechanisms, such as AR splice variants (AR-V7) or mutations, which are not targeted by current ARSIs.
  • Androgen-independent resistance involves the activation of alternative signaling pathways, including DNA repair, PI3K/AKT/mTOR, BRAF-MAPK, Wnt, and glucocorticoid receptor pathways.
  • These alternative pathways can restore downstream signaling, bypassing AR inhibition.

Conclusions:

  • Resistance to ARSIs in prostate cancer is a complex process involving multiple molecular mechanisms.
  • Targeting AR-V7 and exploring inhibitors of alternative signaling pathways are critical areas for future research.
  • Ongoing clinical trials aim to develop strategies to overcome these resistance mechanisms and improve patient outcomes.
Keywords:
androgen receptorcastrate-resistant growthcell signalingcytokinesglucocorticoid receptorlineage plasticitymetastasesneuroendocrine differentiationpharmacological targetingprostate cancerprostate cancer stem cellstransmembrane receptors

More Related Videos

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

7.0K
Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses08:36

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

Published on: October 24, 2019

11.3K

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...
7.9K
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...
7.1K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
3.1K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
13.3K
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
9.8K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K