R417 ‐ The Akt Pathway as a Biomarker in Carcinogenesis

Abstract

Problem The only definitive end point for studies of chemoprevention is the determination of the incidence of primary or secondary cancers which would require a multi-year study with thousands of subjects and tremendous costs. The identification and validation of intermediate endpoints would be an important step in evaluating chemopreventive agents. We have previously noted that curcumin, an exciting nutraceutical with promising chemopreventive effects in HNSCC, inhibited the Akt pathway. Hence we wanted to determine if there was a difference in expression of pAkt in tumors and adjacent mucosa of HNSCC patients when compared to non cancer patients. Methods 16 HNSCC and 16 non-cancer (sleep apnea) patient samples were analyzed by western blot for expression of phosphorylated Akt (pAkt(Ser473)). The SCC samples include tumors and adjacent mucosa. Results Phosphorylated Akt was elevated 12-fold in tumor samples compared to non-cancer patients. No expression of pAkt was seen in mucosa of 12/16 non-cancer patients while tumors and adjacent mucosa express pAkt in 15/16 HNSCC patients (p<0.05). Conclusion The pAkt/mTOR pathway may be sensitive as Akt/mTOR is activated in 99% of HNSCC and not uvulas suggesting pAkt is a good biomarker for a chemopreventive agent. Significance This preferential activation of the Akt pathway in HNSCC compared with the non-cancer patients could be useful in the design of clinical trials with curcumin. Support This work was supported by the Feist-Weiller Cancer Center and the American Society of Hematology.