mTOR inhibitors for treatment of low-risk prostate cancer

Med Hypotheses. 2018 Aug:117:63-68. doi: 10.1016/j.mehy.2018.06.004. Epub 2018 Jun 5.

Abstract

Prostate cancer incidence increases with age; along with many other cancers, it could be considered a disease of aging. Prostate cancer screening has led to a significant proportion of men diagnosed with low-grade, low-stage prostate cancer who are now more likely to choose an active surveillance strategy rather than definitive treatments. Definitive treatment, such as surgery and radiation therapy, is useful for high-grade disease; however, because of the low long-term risk of progression of a low-grade disease and side effects of surgery and radiation, these treatments are less commonly used for low-grade disease. While five alpha reductase inhibitors have been shown to reduce the risk of cancer detection on subsequent biopsies for men on active surveillance, no medications have been proven to prevent progression to high-grade disease. mTOR pathways have long been known to influence prostate cancer and are targets in various prostate cancer patient populations. Low-dose mTOR inhibition with rapamycin has shown promise in pre-clinical models of prostate cancer and appear to affect cellular senescence and immunomodulation in the aging population. We hypothesize that low-dose mTOR inhibition could reduce progression of low-grade prostate cancer patients, allowing them to remain on active surveillance.

MeSH terms

  • 5-alpha Reductase Inhibitors / pharmacology*
  • Aged
  • Animals
  • Cell Line, Tumor
  • Cellular Senescence
  • Disease Progression
  • Early Detection of Cancer
  • Glucose Intolerance
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Middle Aged
  • Models, Theoretical
  • Prostate / pathology
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Androgen / metabolism
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • 5-alpha Reductase Inhibitors
  • Receptors, Androgen
  • MTOR protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Prostate-Specific Antigen
  • Sirolimus