Thephosphatidylinositol-3-kinase/proteinkinase(PI3K/PKB)signalingpa- way—also known as the survival or anti-apoptotic pathway—plays an - portant role in controlling cell growth, proliferation and survival. Whatever the mechanism, the prevalence of PI3K/PKB signaling abnormalities in - man cancers and its potential biological effects (e. g., competitive growth advantage, evasion from apoptosis and therapy resistance) has suggested the potential use of PI3K/PKB pathway modulators as novel targeted therapeutic agents. Following this strategy, a number of compounds have demonstrated antitumor activity in preclinical and clinical settings by targeting directly or indirectly the different components of this pathway. This work covers - cent salient medicinal chemistry achievements in the identi?cation of these pathway modulators, updating recent reports on this class of potential c- cer drugs [1–4]. To help the reader, each section of this piece of work starts with a brief background to understand the target rationale and then moves on to the lead discovery, drug optimization, and clinical results stages as - propriate. A schematic representation of signaling through this pathway and the pathway components covered herein are shown in Fig. 1. Fig. 1 Schematic representation of signaling through the PI3K/PKB pathway 172 C. Garcia-Echeverria 2 Insulin-likeGrowthFactorI Receptor The Insulin-like Growth Factor-I Receptor (IGF-IR) is a member of the - sulin receptor family of tyrosinekinases. This transmembrane-spanning p- tein is composed of two ?-andtwo ?-subunits linked by disul?de bonds.
In each volume an overview chapter introduces the newcomer to the topic coveredSeries covers hot topics of frontier research summarized by reputed scientists in the fieldReview series is topic relatedOnline version available on SpringerLink: springerlink.com