Reviews:
mTOR pathway in colorectal cancer: an update
Maria Giovanna Francipane1,2 and Eric Lagasse1
1 McGowan Institute for Regenerative Medicine, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
2 Ri.MED Foundation, Palermo, Italy.
Correspondence:
Eric Lagasse, email:
Keywords: mTOR, colorectal cancer, cancer stem-like cells, personalized medicine.
Received: October 28, 2013 Accepted: December 3, 2013 Published: December 5, 2013
Abstract
The mammalian target of rapamycin (mTOR) has emerged as a potential target for drug development, particularly due to the fact that it plays such a crucial role in cancer biology. In addition, next-generation mTOR inhibitors have become available, marking an exciting new phase in mTOR-based therapy. However, the verdict on their therapeutic effectiveness remains unclear. Here we review phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling as one of the primary mechanisms for sustaining tumor outgrowth and metastasis, recent advances in the development of mTOR inhibitors, and current studies addressing mTOR activation/inhibition in colorectal cancer (CRC). We will also discuss our recent comparative study of different mTOR inhibitors in a population of colon cancer stem cells (CSCs), and current major challenges for achieving individualized drug therapy using kinase inhibitors.