Cutts - Cellular responses to anticancer drugs
Dr Suzanne Cutts
Senior Research Fellow, College of Science, Health and Engineering
The anticancer drugs doxorubicin (an "anthracycline") and mitoxantrone (an "anthracenedione") are widely used in cancer chemotherapy, and are classified as inhibitors of topoisomerase II. We strive to develop new therapeutic strategies for cancer treatment by understanding the mechanism of action of these currently used anticancer drugs, and building on this information to restrict their killing properties to cancerous cell types. In this way, the toxic side effects of these drugs can be minimised.
It is now well established that anthracyclines such as doxorubicin can bind covalently to DNA to form DNA adducts when activated by the simple molecule formaldehyde. We can activate doxorubicin to bind covalently to DNA in this manner by supplementing with low toxicity formaldehyde-releasing prodrugs. These lesions provide a more lethal death-inducing signal in cells than damage which occurs in the absence of formaldehyde (ie topoisomerase II-mediated damage). The combination of anthracyclines with formaldehyde-releasing agents may prove clinically beneficial.