A drug called Elesclomol blocks an essential pathway in cancer cells that results in their death, a new study says.
Cancer cells break down more glucose than normal cells by a process called glycolysis. The observation, called the Wadburg effect, has been known for almost 60 years now. However, recent studies have shown that cancer cells undergo certain other metabolic pathways that differ from those occurring in normal cells.
Researchers found that cancer cells exhibit higher levels of glycolysis than normal cells and the cells didn't stop at one process alone. "But we also found, surprisingly, that these cells have higher rates of oxidative phosphorylation – they are producing energy through more than one pathway, which explains a lot about how the drug works," says Dr. Stergios Moschos, medical oncologist from UNC.
Researchers now try to tap in these differences and target the pathways that are mostly seen in cancer cells.
In the present study, researchers suppressed oxidative phosphorylation by using the drug Elesclomol. They found that the drug blocks this pathway that is used by the cancer cells to convert nutrients into energy. When this process is halted, the cells no longer survive. Researchers have found that the drug can destroy cells in metastatic melanoma - the stage where the cancer has spread to other parts of the body.
About four years ago, FDA had stopped clinical trials on the drug because the agency felt that the drug along with other drugs can have a negative effect on patients with high serum LDH levels. Levels of LDH can show whether there is tissue damage, abnormal tissue formation, lack of oxygen, etc. The drug was, however, effective in patients who have normal LDH levels.
"Our results suggest that targeting oxidative phosphorylation in melanoma is a promising strategy for early metastatic disease, before melanoma cells switch their primary metabolic source to glycolysis, as Otto Warburg showed 60 years ago" said Dr. Moschos.
Furthermore, the researchers were able to describe why certain cancer cells are resistant to Elesclomol. Long–term exposure to the drug leads to selection of cancer cells that can break down large amount of glucose. They say that a cancer treatment strategy that stops various metabolic pathways can help destroy the cancer cells.
The study is published in the journal PLOS ONE.