mTOR pathway in colorectal cancer: an update

// Maria Giovanna Francipane 1,2 and Eric Lagasse 1 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(definition), 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(definition) (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.