Combo therapy against drug-resistant cancers
doi:10.1038/nindia.2016.127 Published online 29 September 2016
Combining camptothecin, a well-known anticancer alkaloid, with veliparib, an anticancer agent still under clinical trial, researchers have reported good results in treating drug-defying cancers of the breast, ovary, lungs and colon1.
The combination therapy kills the cancer cells by inhibiting the activity of two key enzymes that orchestrate DNA replication, protein synthesis and DNA repair in the cell’s nucleus.
Scientists from Kolkata-based Indian Association for the Cultivation of Science used the drug combination on cell cultures to find that it selectively killed cancer cells and spared the healthy ones. The scientists say these insights could be useful for devising new chemotherapy using drugs that are undergoing clinical trials for a host of cancers.
Previous studies had shown that camptothecin and its derivatives arrest the growth of cancer cells by blocking the activity of DNA topoisomerase 1 (Top1), a nuclear enzyme that aids in DNA replication and protein synthesis. Clinical trials show that veliparib can kill cancer cells by inhibiting another nuclear enzyme poly (ADP) ribose polymerases (PARP) that senses DNA strand breaks and repairs them.
Using cultured colon cancer cells and live-cell imaging, the researchers found that veliaparib markedly enhanced the anticancer efficiency of camptothecin, resulting in increased toxic effects on the cancer cells. In addition, the drug combination can kill cancer cells at low doses, offering a way to overcome the toxic effect of high doses.
1. Das, S. K. et al. Poly (ADP-ribose) polymers regulate DNA topoisomerase I (Top1) nuclear dynamics and camptothecin sensitivity in living cells. Nucleic Acids. Res. (2016) doi: 10.1093/nar/gkw665