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Addressing the Reciprocal Crosstalk between the AR and the PI3K/AKT/mTOR Signaling Pathways for Prostate Cancer
Fabio Raith1, Daniel H O'Donovan1, Clara Lemos2
1Research & Development, Pharmaceuticals, Bayer AG, Müllerstr. 178, 13353 Berlin, Germany.
International Journal of Molecular Sciences
|February 11, 2023
Summary
Prostate cancer resistance emerges from androgen receptor (AR) pathway alterations and PI3K/AKT/mTOR activation. Combination therapies targeting both pathways are crucial for improved treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Androgen receptor (AR) signaling is a primary target in prostate cancer treatment.
- Treatment resistance develops due to AR pathway alterations and activation of alternative pathways like PI3K/AKT/mTOR.
- Crosstalk between AR and PI3K/AKT/mTOR pathways promotes tumor progression and recurrence.
Purpose of the Study:
- To review recent data on the crosstalk between AR and PI3K/AKT/mTOR signaling in prostate cancer.
- To discuss selective inhibitors targeting these pathways and their clinical applications.
- To highlight the need for novel combination approaches and predictive biomarkers.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of molecular mechanisms underlying treatment resistance.
- Evaluation of current and emerging therapeutic strategies.
Main Results:
- Alterations in AR and PI3K/AKT/mTOR pathways are key drivers of prostate cancer progression and resistance.
- Existing PI3K/AKT/mTOR inhibitors show limited benefit in prostate cancer due to side effects.
- Combination therapies targeting both AR and PI3K/AKT/mTOR pathways show promise.
Conclusions:
- Understanding the intricate crosstalk between AR and PI3K/AKT/mTOR pathways is vital for overcoming treatment resistance.
- Development of novel combination therapies and predictive biomarkers is essential for improving patient outcomes in prostate cancer.
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