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The PI3K Pathway in Colorectal Cancers

  • Jihye Yun
  • George Poulogiannis
  • Evan T. Brower
  • Samuel Klempner
  • Lewis L. Cantley
Chapter

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.

Keywords

Vascular Endothelial Growth Factor Epidermal Growth Factor Receptor Mutant Epidermal Growth Factor Receptor mTOR Inhibitor PI3K Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jihye Yun
    • 1
    • 2
    • 3
  • George Poulogiannis
    • 2
    • 3
  • Evan T. Brower
    • 4
  • Samuel Klempner
    • 5
  • Lewis L. Cantley
    • 1
    • 2
    • 3
  1. 1.Department of MedicineWeill Cornell Medical CollegeNew YorkUSA
  2. 2.Department of Medicine, Division of Signal TransductionBeth Israel Deaconess Medical CenterBostonUSA
  3. 3.Department of Systems BiologyHarvard Medical SchoolBostonUSA
  4. 4.Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreUSA
  5. 5.Division of Hematology-OncologyBeth Israel Deaconess Medical CenterBostonUSA

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