Overcoming resistance to anti-cancer drugs by targeting cell 'powerhouses'

Shana Kelley and colleagues explain that doxorubicin and other common forms of chemotherapy work by damaging the genes inside the nucleus of cancer cells. Cancer cells divide and multiply faster than surrounding normal cells, making copies of their genes. The drugs disrupt that process. But cancer cells eventually adapt, developing structures that pump out nucleus-attacking drugs before they can work. Kelley's team explored the effects of targeting doxorubicin to the mitochondria, the energy-producing structures in cells that also contain genes.

They describe a re-targeting approach that involved mating doxorubicin with a small piece of protein that made the drug travel to mitochondria instead of the nucleus. The combo killed cancer cells, even those that had developed pumps. Such an approach could work with a whole family of anti-cancer drugs that target the nucleus, the scientists indicate.

The authors acknowledge funding from the Canadian Institutes of Health Research.