Synergizing Drugs Show Effectiveness against Skin Cancer

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Melanoma responds best to a class of drugs called protein kinase inhibitors. Unfortunately, in many cases, the mutated cells become resistant to treatment and the patient relapses. Now MIT researchers suggest that combining existing medication with experimental drugs could lead to better results.

We discovered that this ribonuclease drug could be paired favorably with other cancer chemotherapeutic agents, and not only that, the pairing made logical sense in terms of the underlying biochemistry”, says Ronald Raines, Professor of Chemistry at Massachusetts Institute of Technology.

Ribonucleases are enzymes that break down RNA that is no longer needed and help to defend against viral RNA. Finding a way of harnessing these abilities and utilizing them against cancerous cell could represent an important weapon against malignancy.

Published in the Molecular Cancer Therapeutics journal, the study describes how the ribonuclease inhibitor protein produced in human cells had phosphate groups attached to it, making the bind stronger. Phosphorylation was being carried out by protein kinases that are part of a cell signaling pathway called ERK. It controls how cells respond to growth factors and are overactive in tumors. The combinations of trametinib and dabrafenib were able to shut off the ERK pathway.

This was a fortuitous intersection of two different strategies, because we reasoned that if we could use these drugs to deter the phosphorylation of ribonuclease inhibitor, then we could make the ribonucleases more potent at killing cancer cells”, noted Raines.

Not only is the resulting treatment more efficient at destroying the mutated cells, but it seems this approach could also lead to reduced side effects and a lower chance of tumors becoming drug-resistant.

We’re hoping that we can explore relationships with some of the many pharmaceutical companies that develop ERK pathway inhibitors, to team up and use our ribonuclease drug in concert with kinase inhibitors”, added Dr. Ronald.

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