Dr Lewis is investigating two enzymes called CYP1A1 and CYP1A2, which activate DTIC into its chemotherapy form in the body.
DTIC works through a natural process where the drug is switched on in the parts of the body where the enzymes are active and then flags those cells for destruction. Unfortunately because of the abundance of the CYP1A2 enzyme in the liver, the drug is released into the body’s broader circulation, causing substantial toxicity.
Dr Lewis has identified that the CYP1A1 enzyme is not found in the liver and could therefore be more efficient in activating the drug with less adverse effects. With funding from the FMC Foundation, he aims to use gene therapy to deliver enhanced CYP1A1 enzymes to targeted tissues or tumours together with another molecule that will deactivate CYP1A2, thus preventing toxicity in the liver and broader circulation.
This approach could ensure that this chemotherapy is more successfully targeted to the cancer and not surrounding tissues and organs, thereby improving the treatment and alleviating many adverse effects.
As DTIC is also traditionally used for the treatment of intracranial carcinoma, neuroblastoma, soft tissue sarcoma, Hodgkin’s disease and neuroendocrine tumours, it could also lead to improved treatments for many cancer types.
In his spare time, Dr Lewis is an avid cyclist and will be undertaking the 200km Ride to Conquer Cancer challenge this year to help raise funds for the vital work underway at the FCIC. To donate to Ben, the FMC Foundation Team, or another rider please visit www.conquercancer.com.au.