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Cancer Drug 49 Times More Potent Than Cisplatin

Osmium compound shuts down energy production in cancer cells

Tests conducted at the University of Warwick in the United Kingdom have shown that a new cancer drug, FY26, is 49 times more potent than the clinically used treatment cisplatin.

Based on a compound of the rare precious metal osmium, FY26 shuts down cancer cells by exploiting weaknesses inherent in their energy generation.

The researchers argue that the drug could be cheaper to produce and less harmful to healthy cells compared with existing treatments. FY26 is also active against cancer cells that have become resistant to platinum-based drugs.

The experiments, involving 809 cancer cell lines, found that FY26 was 49 times more potent than cisplatin. Similar results were obtained by the National Cancer Institute in tests conducted on 60 cell lines.

The new drug works by forcing cancer cells to use their mitochondria, the “powerhouse” of cells, to generate the energy necessary to function. While healthy cells use mitochondria to generate energy, cancer cells contain defective mitochondria that are incapable of sustaining the cell’s energy requirements. In the absence of FY26, cancer cells switch from using their defective mitochondria to using glycolysis in their cytoplasm to generate energy. By stopping this switch of energy sources, FY26 causes cancer cells to die.

Commenting on the drug’s benefits compared with those of existing platinum-based treatments, such as cisplatin, lead investigator Professor Peter Sadler said: “Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens and exert their activity by damaging DNA, and they cannot select between cancerous and noncancerous cells. This can lead to a wide range of side effects, from renal failure to neurotoxicity, ototoxicity, nausea, and vomiting.”

“Existing platinum-based cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked, but our new osmium compound, with its different mechanism of action, remains active against cancer cells that have become resistant to drugs such as cisplatin,” he added.

The research could also lead to substantial improvements in cancer survival rates, according to co-researcher Dr. Isolda Romero-Canelon. “Current statistics indicate that one in every two people will develop some kind of cancer during their lifetime,” she remarked. “It is clear that a new generation of drugs is necessary to save more lives, and our research points to a highly effective way of defeating cancerous cells.”

The research was published in the Proceedings of the National Academy of Sciences.

Following the successful test results, the investigators have been awarded a grant to begin preclinical development of organo-osmium compounds.

Source: EurekAlert; July 7, 2015.

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