Cancer cells acquire the ability to circumvent the normal checks and balances placed on cells, resulting in uncontrolled growth. This is particularly relevant in the case of targeted therapies. While initially a tumor may respond to a particular drug targeting one pathway, eventually the tumor cells find “alternate” pathways to survive.
One focus of the Keri lab attempts to identify combinations of drugs that target intersecting pathways required for breast cancer growth and survival. The PI3K/AKT/mTOR pathway provides the major growth/survival signal in a cell and is one of the most frequently hyperactivated pathways in breast cancer. Drugs targeting this pathway alone have shown limited clinical efficacy, in part, due to loss of pathway feedback inhibition.
We have identified the src-family kinases (SFKs) as members of an intersecting pathway that, when targeted together with the mTOR pathway, have the potential to improve the efficacy of mTOR inhibitors, restoring this feedback control and inducing tumor regression. Future studies are aimed at delineating the precise mechanism of these pathway interactions as well as investigating the utility of this and other drug combinations in multiple types of cancer.