**Targeting the PI3K/AKT/mTOR Pathway in Cancer Cells**

Isabella S. Guimarães, Nayara G. Tessarollo, Paulo C.M. Lyra-Júnior, Diandra Z. dos Santos, Roger C. Zampier, Laura F.R.L. de Oliveira, Krislayne V. Siqueira, Ian V. Silva and Leticia B.A. Rangel

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61676

#### **1. Introduction**

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128 Updates on Cancer Treatment

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a critical regulator of many essential physiological processes, but it also plays a key role in the malignant transformation of human tumors and their subsequent growth, metabolism, proliferation, and metastasis [1]. Previous studies have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in human cancers due to the somatic mutation and amplification of genes encoding key components [2,3]. In addition, aberrant PI3K/AKT/mTOR signaling activation also confers resistance to conventional therapies and is a poor prognostic factor for many types of cancers [4,5]. Several agents that target the PI3K/AKT/mTOR cascade elements are undergoing evaluation in preclinical and clinical studies. These include PI3K inhibitors, AKT inhibitors, mTOR catalytic site inhibitors, and dual PI3K-mTOR inhibitors. This chapter focuses on recent preclinical and clinical data on the efficacy of PI3K/AKT/mTOR pathway inhibitors either as monotherapy or in combination with conventional chemotherapy or others target drugs. Herein, we review four different classes of PI3K pathway inhibitors: PI3K inhibitors, AKT inhibitors, mTOR catalytic site inhibitors, and dual PI3K-mTOR inhibitors.
