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The PI3K Pathway in Colorectal Cancers

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Molecular Pathogenesis of Colorectal Cancer

Abstract

Phosphoinositide 3-kinase (PI3K) belongs to the intracellular lipid kinases family involved in diverse physiological processes, including proliferation, apoptosis, growth, and metabolism. Recent mutation analysis has shown that the PI3K pathway is one of the most frequently dysregulated pathways in human cancer, including colorectal cancer (CRC). Accordingly, significant effort has been made to develop pharmacological inhibitors targeting PI3K or key nodes in this pathway, such as AKT and mTOR. There are currently more than 20 unique compounds targeting the PI3K pathway being assessed in numerous cancer-related clinical trials. In addition, the mutation status of PI3K pathway in cancers may have predictive and prognostic implications. After 3 decades of the discovery of PI3K, we are now at an exciting intersection in translating our knowledge of the PI3K signaling pathway into developing effective therapeutics for the treatment of cancer. A comprehensive understanding of circuits and regulations of this pathway are essential to the rational development of such therapies. In this chapter, we will discuss recent advances in our understanding of the functions and mutations of PI3K signaling pathway in the pathogenesis of CRC. We will also review current drug-discovery efforts and challenges targeting PI3K signaling for the treatment of CRC.

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Authors and Affiliations

  1. Department of Medicine, Weill Cornell Medical College, New York, NY, 10065, USA

    Jihye Yun & Lewis L. Cantley

  2. Department of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA

    Jihye Yun, George Poulogiannis & Lewis L. Cantley

  3. Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA

    Jihye Yun, George Poulogiannis & Lewis L. Cantley

  4. Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA

    Evan T. Brower

  5. Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA

    Samuel Klempner

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  1. Jihye Yun
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  2. George Poulogiannis
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  3. Evan T. Brower
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  4. Samuel Klempner
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  5. Lewis L. Cantley
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Correspondence to Lewis L. Cantley .

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  1. Molecular Pathology Unit, Harvard Medical School, Charlestown, Massachusetts, USA

    Kevin M. Haigis, Ph.D.

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Yun, J., Poulogiannis, G., Brower, E.T., Klempner, S., Cantley, L.L. (2013). The PI3K Pathway in Colorectal Cancers. In: Haigis, Ph.D., K. (eds) Molecular Pathogenesis of Colorectal Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8412-7_6

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