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Updated: Oct 7, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Overview of the Development and Use of Akt Inhibitors in Prostate Cancer

Anis Gasmi1, Guilhem Roubaud2, Charles Dariane3

  • 1Department of Urology, University of Rennes, 35000 Rennes, France.

Journal of Clinical Medicine
|January 11, 2022
PubMed

Insights

The PI3K-Akt-mTOR pathway is crucial in cancer. Akt inhibitors like Ipatasertib show promise for metastatic prostate cancer with PTEN loss when combined with androgen deprivation therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway is frequently dysregulated in various cancers.
  • In prostate cancer, loss of phosphatase and tensin homolog (PTEN) function is a key driver of pathway activation.
  • Developing selective Akt inhibitors has historically presented significant challenges.

Purpose of the Study:

  • To evaluate the efficacy of Akt inhibitors in combination with androgen deprivation therapies for prostate cancer.
  • To investigate the role of PTEN loss in response to Akt inhibition.
  • To summarize recent clinical trial findings for Akt inhibitors in metastatic castration-resistant prostate cancer.

Main Methods:

  • Review of recent phase II and III clinical trials.
  • Analysis of treatment outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC).
  • Focus on trials involving specific Akt inhibitors (Ipatasertib, Capivasertib) and PTEN-loss status.

Main Results:

  • Ipatasertib and Capivasertib, when combined with androgen deprivation therapies, demonstrated promising outcomes in mCRPC patients with PTEN-loss.
  • These combinations showed potential in a challenging patient population.
  • Ongoing trials continue to explore various Akt inhibitors and combinations across different disease stages.

Conclusions:

  • Akt inhibitors represent a promising therapeutic strategy for prostate cancer, particularly in cases of PTEN loss.
  • Combination therapy with androgen deprivation holds significant potential for improving outcomes in mCRPC.
  • Further clinical investigation is warranted to optimize the use of Akt inhibitors in prostate cancer treatment.
Keywords:
AktCapivasertibIpatasertibPTENcastration resistanceprostate cancer

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