Lilly/TGen identify potential novel cancer target

Researchers from US drug major Eli Lilly and the Phoenix-based Translational Genomics Research Institute (TGen) have identified a novel recurring mutation of the gene AKT1 in breast, colorectal and ovarian cancers. The altered form of AKT1 appears to cause tumor cell proliferation and may play a role in making cells resistant to certain types of therapies. The findings are reported in an advance on-line publication of the journal Nature.

The PI3-Kinase/AKT pathway is among the most commonly activated cellular pathways in human cancers and members of this pathway are among the most frequently targeted for new oncology drug discovery efforts. Activation of this pathway results in cancer cell growth and cell survival. Although AKT1 is central to pathway activation, its role in cancer has been identified as that of an intermediary between mutated upstream regulatory proteins and downstream survival signaling proteins. Lilly noted that this is the first evidence of direct mutation of AKT1 in human cancer tumors: it was discovered in clinical samples from cancer patients, yet has never been detected in cancer cell lines.

John Carpten, director of TGen's Integrated Cancer Genomics Division and the study's lead author, said that "the next step is to determine the prevalence of the AKT1 mutation in different populations and, hopefully, use the information gained to stratify patients going into clinical trials for AKT inhibitors." If validated by further studies, the identification of this recurring mutation has the potential to impact cancer treatment and drug development, Lilly added.