AR and PI3K/AKT in Prostate Cancer: A Tale of Two Interconnected Pathways

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Prostate cancer (PCa) is a leading cancer in men, with the androgen receptor (AR) driving its progression.
• Androgen receptor signaling inhibitors (ARSIs) show efficacy in castration-sensitive PCa (CSPC), but resistance leads to poor outcomes in castration-resistant PCa (CRPC).
• Mechanisms of ARSI resistance include AR mutations and hyperactivation of alternative pathways like PI3K/AKT/mTOR.

Purpose of the Study:

• To review current AR and PI3K/AKT/mTOR signaling pathway inhibitors in PCa treatment.
• To analyze treatment outcomes of monotherapy and combination strategies in preclinical and clinical trials.
• To highlight the crosstalk between AR and PI3K signaling pathways in PCa.

Main Methods:

• PubMed literature search up to November 2022 for relevant articles.
• Selection of recent and pertinent studies on AR and PI3K signaling in PCa.
• Utilized ClinicalTrials.gov for clinical study information and results.

Main Results:

• Significant interaction identified between AR and PI3K/AKT/mTOR pathways in PCa.
• Various AR and PI3K inhibitors show promise as monotherapy or in combination.
• Data from preclinical and clinical trials are being compiled to assess treatment efficacy.

Conclusions:

• Targeting the interplay between AR and PI3K/AKT/mTOR pathways is crucial for overcoming ARSI resistance in PCa.
• Combination therapies involving AR and PI3K inhibitors represent a promising strategy for advanced PCa.
• Further clinical investigation is warranted to optimize treatment regimens and improve patient prognosis.