East Montgomery Times

Researchers at the Fox Chase Cancer Center have recently released two comprehensive reviews on the role of AKT, also known as protein kinase B, in cancer development and treatment. The reviews highlight AKT's significant influence on cellular functions such as survival, proliferation, and growth, and its potential impact when it becomes deregulated.

The 1991 study from Fox Chase first identified AKT's involvement in malignancy, marking a pivotal moment in cancer research. This study led to extensive investigations into AKT as a retroviral oncoprotein and novel signaling kinase. "There was no doubt that this protein was relevant for cancer and various other processes," said Bellacosa.

A landmark paper from Tsichlis' lab published in Cell in 1995 further positioned AKT within the PI3K pathway, crucial for cellular physiology. Deregulation of this pathway is critical in cancer development.

Subsequent research linked alterations of AKT to ovarian cancer. Testa and Bellacosa assert that these findings are now being realized through clinical trials using small-molecule inhibitors targeting the AKT pathway. "Excitingly, research published just a few months ago showed that AKT inhibitors have a positive effect in patients with triple-negative breast cancer," Bellacosa noted.

The new reviews discuss the therapeutic significance of AKT inhibitors, including their combination with immunotherapies. They emphasize how targeting the AKT pathway could be an effective strategy against cancer due to its involvement in all 14 hallmarks of cancer biology proposed by Hanahan and Weinberg.

"Recently, it has become increasingly clear that the AKT pathway plays a critical role in many aspects of cancer," Testa stated. He added that there is now significant interest in targeting this pathway as a rational therapeutic strategy due to its frequent involvement across various cancers.

Bellacosa's review was published in the Journal of Experimental and Clinical Cancer Research, while Testa's review appeared in Cancer Research. Both papers underscore innovative approaches to specifically target mutant forms of AKT with minimal side effects on glucose homeostasis. "These new mutant-selective inhibitors are expected to dramatically improve the treatment of cancers fueled by mutant AKT alleles," Bellacosa explained.