Researchers from University of Salford identify gene that causes cancer drug resistance
The research team from University of Salford have recently identified a key protein which is believed to be a leading causes of resistance tamoxifen, a commonly used drug cancer.
Throughout patient treatment, around half of those are administered tamoxifen, a treatment which blocks oestrogen receptors as part of its mechanism of action. Although the cancer has started to become resistant to its effects. The researchers believed this could be related to energy-generating mitochondria within cancer cells; by comparing the cells that are resistant to tamoxifen to those which were still sensitive, the researchers discovered that the key difference was mitochondrial power.
Through a process of genetics, metabolism and protein profiling, the team identified the protein NQ01 as the driving force in resistance to the drug, noting that by chemically inhibiting it, tamoxifen-resistant cells could be desensitised.
“In simple terms, the process of poisoning the cell (with tamoxifen) actually has the opposite effect, stimulating the cancer cells to respond by revving their engines in order to survive.” Michael P Lisanti, Professor of Translational Medicine in the Biomedical Research Centre at the University of Salford, explained. “This is the first evidence that tamoxifen resistance is related to a specific metabolic behaviour, i.e. increased mitochondrial power, which is important because this is not related to tamoxifen’s effect on the oestrogen receptor. It also confirms that tamoxifen resistance is not a mechanism related to oestrogen.”
Co-author Dr Marco Fiorillo added: “Now that we have identified the target, this will allow us and others to design new drugs to overcome tamoxifen resistance. There are already existing experimental drugs for targeting NQO1 and GCLC, for other reasons, so making inhibitors to target these enzymes is a practical reality.”