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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Regulation and Importance of the PI3K/Akt/mTOR Signaling Pathway in Hematologic Malignancies

Author(s): Kiyotaka Kawauchi, Toshie Ogasawara, Masako Yasuyama, Kuniaki Otsuka and Osamu Yamada

Volume 9, Issue 9, 2009

Page: [1024 - 1038] Pages: 15

DOI: 10.2174/187152009789377772

Price: $65

Abstract

Phosphatidylinositol 3-kinase (PI3K), a heterodimeric lipid kinase, is a key enzyme in signal transduction from various stimuli to downstream pathways that elicit diverse responses involving growth, proliferation, survival, differentiation, and metabolism in many cellular systems. Activated PI3K generates phosphatidylinositol-3,4,5-triphosphate, which recruits phosphatidylinositol-dependent kinase 1 (PDK1) and Akt serine/threonine kinase at the plasma membrane, resulting in activation of Akt. In turn, Akt activates multiple downstream targets, most notably the mTOR pathway. There is abundant evidence implicating the PI3K/Akt/mTOR pathway in the development and progression of a variety of tumors including hematologic neoplasms. Therefore, this pathway is considered a critical target for cancer therapy. We review the regulatory mechanisms of the PI3K/Akt/mTOR signaling pathway and the role of this pathway in oncogenesis of hematological malignancies.

Keywords: PI3K, Akt, mTOR, hematologic malignancies


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