ONE of the most harrowing prospects for patients undergoing cancer therapy is that the disease will spiral out of control if tumours develop resistance to standard treatments.
Discovery of a 鈥渞enegade鈥� gene that switches from being a cancer killer to a cancer accomplice could explain why this occurs, and generate better therapies. The gene that changes allegiance makes a receptor that sits on the cell surface and binds to a molecule called the CD95 ligand (CD95L). When CD95L binds to the receptor on normal cells, and on cancer cells sensitive to treatment, it tells the cells to self-destruct.
Common cancer therapies increase production of CD95L. But researchers have now discovered that in many cancer cells that have become resistant to drugs, the CD95 receptor becomes a cancer 鈥減romoter鈥� instead (The EMBO Journal DOI: 10.1038/sj.emboj.7600325).
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Marcus Peter, and his team at the University of Chicago, discovered the receptor鈥檚 dark side after treating drug-resistant cells from 60 different types of human tumours with CD95L. Instead of dying, many grew, and became capable of spreading.
A single mutation in the gene for the receptor triggers the switch in its behaviour, Peter says.
But there is also a positive side to the research. The researchers discovered that the invasive potential of cancer cells with the mutated receptor relies on an enzyme called urokinase plasminogen activator (uPA). When they blocked its activity, the cells ceased to spread.
Peter says that in future, when treating resistant cancers with second-line chemotherapy drugs, it might be possible to block the insidious effects of the renegade receptor by giving uPA blockers as well. A Munich company, Wilex, already has an uPA inhibitor in clinical trials.