With almost 4 million new cases every year, cancer is a leading cause of death and morbidity in Europe. Platinum-based drugs are highly successful as an anticancer treatment and are used in half of all chemotherapies. Andrea Erxleben, the project coordinator of the EU-supported TSPO METALLODRUGS project is on a mission to develop a new generation of these metallodrugs. As effective as they are, metallodrugs come with two principle drawbacks: tumours can become resistant to treatment, and off-target effects can damage healthy cells. “The general approach to reducing the risk of resistance development is to combine two different cancer drugs with independent modes of action,” Erxleben explains. “To reduce side effects, researchers try to use a targeting entity that helps the drug accumulate selectively in tumours cells.” Erxleben is combining both these approaches in a new tranche of anticancer drugs. Platinum’s potential as an anticancer agent was discovered in 1969, and the first drug, cisplatin, approved in 1978. Since then, few new metallodrugs have made it to clinics, with only three available for use and four others in clinical trials. Working out of the National University of Ireland, Galway, Erxleben hopes to bring a fresh perspective to this widely researched field. Metallodrugs are built around individual metal ions. In the case of platinum drugs, the metal entity binds to tumour DNA and prevents it being repaired or replicated, resulting in the death of the cell. As well as platinum, Erxleben and her colleague investigated two other metals known to kill cancer cells, gold and copper. Erxleben combined platinum, gold and copper ions with a molecule that interacts with a protein called TSPO, found on the membranes of mitochondria. “The beauty of this protein is it’s involved in energy metabolism,” says Erxleben: “So we can kill the cancer cell by cutting off its energy supply.” The TSPO protein is overexpressed in many tumours, so the treatment is preferentially delivered to cancerous cells. The metal complex can also be attached to an anticancer drug, delivering a double strike against the tumour. “We have a molecule that interrupts energy metabolism and at the same time can direct the attached anticancer agent to the cell.” This research was undertaken with the support of the Marie Skłodowska-Curie programme. “Without the funding, we could not have done the project,” she explains, adding that the programme helped her to establish collaborations with researchers in the United Kingdom and United States. The investigation into these new metallodrugs is at the proof of concept stage, and if successful it will still be years before they are used clinically. However, work carried out today may one day be used to help save the lives of millions of cancer patients across Europe.
TSPO METALLODRUGS, platinum, gold, copper, Galway, cancer, tumour, chemotherapy, mitochondria