Regulation, Role, and Targeting of Akt in Cancer

The serine-threonine kinase AKT, also known as protein kinase B (PKB), was identified in 1977 as the proto-oncogene of the v-Akt oncogenicmurine thymoma virus.1 Subsequent research has demon-strated that genetic events activatingAktoccur inmost typesof cancer. Activation of Akt promotes many of the processes critical to the malignant phenotype. Thus, Akt is an attractive therapeutic target for cancer. However, its critical role in many physiologic processes sug-gests that achieving an acceptable therapeutic index with Akt inhibi-tors may be a challenge. In Journal of Clinical Oncology, Yap et al2 report the resultsof, toourknowledge, thefirst-in-manphase I clinical trial of Akt inhibitor MK-2206. In addition to determining the maximum-tolerated dose ofMK-2206, the study included a pharma-codynamic analysis of hair follicles in the majority of patients, and of paired tumor biopsies in a maximum-tolerated dose expansion co-hort. The results provide strong evidence that significant inhibition o