Grants - North Carolina - Designated Grants - 2015

John Cavanagh, Ph.D.

Funded by a challenge grant with

North Carolina State University

The Jimmy-NCSU V Cancer Therapeutic Program allows young researchers the opportunity to work on multiple facets of cancer research in a set of diverse labs, each investigating different approaches for developing cancer therapeutics.

Enhancing cancer drugs
We have discovered molecules that increase the effects of anticancer drugs by several orders of magnitude.  Our goal is to reduce the working concentrations of all anti-cancer drugs in order to mitigate serious side effects.  We will develop and screen our new molecules with both novel and existing chemotherapeutics against a variety of cancer cell lines in order to define the optimum combination treatment.  Initial screens show effects against breast, renal and colon cancer cell lines.

Cell death and tumor formation
The life and death of cells must be balanced.  Normal cells accommodate this balance by invoking programmed cell death pathways, referred to as apoptosis.  In cancer cells, these pathways are defective and normal cell death does not occur, leading to tumor formation.  In addition, faulty apoptosis causes tumor cells to be resistant to chemo/radiation therapies.  If we could make apoptosis occur properly, we slow down tumor formation and overcome this resistance.

The protein caspase-3 controls apoptosis.  If caspase-3 fails to function, cell death does not happen correctly.  We also know that the protein calbindin-D28K binds to caspase-3 and stops it functioning.  If we can stop calbindin-D28K from interfering with caspase-3, apoptosis would occur normally and the risk of cancer developing would be reduced.  Consequently calbindin-D28K is a powerful target for anticancer drug development.