Topical treatment for melanoma prevention in the works

A cancer-fighting formulation applied directly to the skin to prevent the development of melanoma lesions is now under study in the laboratory—and demonstrating encouraging results.

Despite the use of sunscreen and the establishment of screening programs for early excision of premalignant lesions, melanoma incidence is on the rise. This indicates a need for additional preventive strategies, according to a team headed by Gavin P. Robertson, PhD, the director of Penn State Hershey Melanoma Center (Hershey, Pennsylvania).

“One unexplored area involves targeting genes whose deregulation promotes disease development to prevent melanoma,” explain the researchers in a Cancer Prevention Research report of their work (2011;4[2]:248-258).

Approximately 70% of melanomas develop when the Akt3 protein prevents apoptosis, or cell death. Inhibiting this defect could help prevent the disease. Naturally occurring compounds called isothiocyanates, which are found in broccoli and other cruciferous vegetables, have been identified as inhibitors of Akt3. However, isothiocyanates have low chemotherapy potency on melanoma cells, and high concentrations are needed to be effective.

To respond to that need, researchers at Penn State Hershey Melanoma Center had previously developed a more potent version of isothiocyanates called isoselenocyanates (ISC-4) by replacing sulfur with selenium. But the chemopreventive potential of ISC-4 was not known.

In the current study, Robertson and associates found that repeated topical application of ISC-4 reduced tumor cell expansion in a laboratory-generated human skin model of melanoma by 80% to 90%, and reduced tumor development in mice carrying invasive xenografted human melanoma by approximately 80%. The treatment killed melanoma cells 2 to 5 times more effectively than it killed normal cells, did no obvious damage to skin cells or skin structure, and did not cause any major organ-related toxicity in the treated animals.

“Mechanistically, ISC-4 prevented melanoma by decreasing Akt3 signaling that lead to a 3-fold increase in apoptosis rates,” concluded the investigators. “Thus, topical ISC-4 can delay or slow down melanocytic lesion or melanoma development in preclinical models and could impact melanoma incidence rates if similar results are observed in humans.”

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