1. ¹Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2. ²Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3. ³Department of Molecular Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Dr JN Myers, Department of Head and Neck Surgery, Unit 441, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. E-mail: jmyers@mdanderson.org

Received 10 November 2004; Revised 17 February 2005; Accepted 24 March 2005; Published online 3 May 2005.

Abstract

The phosphatidylinositol 3' kinase (PI3K)/phosphatase and tensin homologue deleted on chromosome ten/Akt pathway, which is a critical regulator of cell proliferation and survival, is mutated or activated in a wide variety of cancers. Akt appears to be a key central node in this pathway and thus is an attractive target for targeted molecular therapy. We demonstrated that Akt is highly phosphorylated in thyroid cancer cell lines and human thyroid cancer specimens, and hypothesised that KP372-1, an Akt inhibitor, would block signalling through the PI3K pathway and inhibit cell proliferation while inducing apoptosis of thyroid cancer cells. KP372-1 blocked signalling downstream of Akt in thyroid tumour cells, leading to inhibition of cell proliferation and increased apoptosis. As thyroid cancer consistently expresses phosphorylated Akt and KP372-1 effectively blocks Akt signalling, further preclinical evaluation of this compound for treatment of thyroid cancer is warranted.