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Hormone Therapy plus mTOR Inhibitors in the Treatment of Endometrial Carcinoma

Erica M Stringer, Gini F Fleming

    Oncology & Hematology Review
    |November 29, 2014
    PubMed

    Insights

    Progestin therapy shows limited effectiveness for advanced endometrial cancer. Combining hormonal treatment with mTOR inhibitors may improve treatment sensitivity by targeting the PI3K/AKT/mTOR pathway.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Genetics

    Background:

    • Hormonal therapies, like progestins, offer modest benefits for advanced endometrial cancer.
    • Mechanisms underlying progestin resistance are not fully understood.
    • The PI3K/AKT/mTOR pathway is frequently altered in endometrial carcinomas and linked to hormonal therapy resistance.

    Purpose of the Study:

    • To explore the potential of combining hormonal therapy with mTOR inhibitors for endometrial cancer.
    • To investigate if mTOR inhibition can enhance sensitivity to hormonal treatments.

    Main Methods:

    • Analysis of PI3K/AKT/mTOR pathway components and their mutations (PTEN, PIK3CA, PIK3R1) in endometrial carcinomas.
    • Review of existing data on the efficacy of mTOR inhibitors (temsirolimus, everolimus, ridaforolimus) in endometrial cancer.

    Main Results:

    • Mutations in PTEN, PIK3CA, and PIK3R1 are common in endometrial cancer, suggesting PI3K/AKT/mTOR pathway dysregulation.
    • Both hormonal therapies and mTOR inhibitors demonstrate single-agent activity in endometrial cancer.

    Conclusions:

    • Targeting the PI3K/AKT/mTOR pathway with inhibitors may overcome progestin resistance.
    • Combination therapy of hormonal agents and mTOR inhibitors warrants further investigation for advanced endometrial cancer treatment.
    Keywords:
    Endometrial cancereverolimushormone therapyletrozolemTOR inhibitorprogestinridaforolimustemsirolimus

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