Cancer metabolism and redox regulation of chemotherapeutics

Joshua Lewis, Francesco Costantini

Collaborators: Cristina Furdui (Wake-Forest), Dave Boothman (UTSW)

Funding Source: Georgia Cancer Coalition, the Giglio Family Foundation, NCI

Related link: NCI Cancer Systems Biology Consortium

Variations in the distribution of proteins that metabolize foreign molecules can control a cell's ability to respond to chemotherapeutics or environmental toxins. We have used a systems-level approach provides a framework for understanding how patient-specific variability leads to patient sensitivity to chemotherapeutic treatment at different doses. With this knowledge, we have correctly predicted complex behavior induced by pharmacological intervention strategies for manipulation of drug metabolism.

We have also investigated the role of antioxidant genes in the shift and stability of phenotypes associated with cancer cell transdifferentiation. We recently explored the dual role of antioxidant transport and drug efflux in defining "cancer stem cells" known as side populations.