MicroRNAs and the cellular response to rapamycin: Potential role in diagnosis and therapy

Totary-Jain, Hana; Marks, Andrew R.

The mammalian target of rapamycin (mTOR) is a major regulator of cell
growth, motility and angiogenesis that is often deregulated in malignancies. mTOR inhibitors have been approved for the treatment of renal cell carcinoma and mantle cell lymphoma. Currently, second generation mTOR inhibitors are under clinical evaluation. Major challenges remain in the identification of patients who will respond to mTOR inhibitors and the development of therapeutics that can overcome intrinsic resistance or acquired resistance. There are currently no biomarkers that predict tumor response to mTOR inhibitors.
MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene expression. MiRNAs participate in many biological processes including proliferation and apoptosis. miRNAs are often deregulated in cancer and act as tumor suppressors or oncogenes.2 Recently miRNAs emerged as diagnostic and prognostic markers to assess therapeutic responses giving rise to the field of miRNA pharmacogenomics.3 Numerous studies indicate that mTOR and its signaling pathway is regulated by miRNAs. However, little is known as to whether miRNAs play a role in the intrinsic tumor resistance or the development of acquired resistance to mTOR inhibitors.
In our recent studies we used rapamycin resistant (RR1) variants of the murine brain tumor cell line BC3H1, developed by chronic rapamycin treatment.


Also Published In

Cell Cycle

More About This Work

Academic Units
Physiology and Cellular Biophysics
Published Here
July 11, 2013