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Br J Clin Pharmacol. 2016 Nov;82(5):1180-1188. doi: 10.1111/bcp.12844. Epub 2015 Dec 26.

Therapeutic potential of mTOR inhibitors for targeting cancer stem cells.

Author information

1
McGowan Institute for Regenerative Medicine, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA. francipa@pitt.edu.
2
Ri.MED Foundation, 90133, Palermo, Italy. francipa@pitt.edu.
3
McGowan Institute for Regenerative Medicine, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.

Abstract

The mammalian target of rapamycin (mTOR) pathway is aberrantly activated in many cancer types. As the intricate network of regulatory mechanisms controlling mTOR activity is uncovered, more refined drugs are designed and tested in clinical trials. While first generation mTOR inhibitors have failed to show clinical efficacy due partly to the feedback relief of oncogenetic circuits, newly developed inhibitors show greater promise as anti-cancer agents. An effective drug must defeat the cancer stem cells (CSCs) while sparing the normal stem cells. Due to its opposing role on normal and malignant stem cells, mTOR lends itself very well as a therapeutic target. Indeed, a preferential inhibitory effect on CSCs has already been shown for some mTOR inhibitors. These results provide a compelling rationale for the clinical development of mTOR-targeted therapies.

KEYWORDS:

cancer stem cells, drug resistance; mTOR; personalized medicine; tumour heterogeneity

PMID:
26609914
PMCID:
PMC5061787
DOI:
10.1111/bcp.12844
[Indexed for MEDLINE]
Free PMC Article

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