Feb. 23 (UPI) -- Researchers at The Wistar Institute in Philadelphia have found an anti-diabetic drug activates an anti-aging gene that can inhibit growth of melanoma in older patients.
Melanoma, a form of skin cancer, is more frequently diagnosed in older patients. Current targeted therapies to treat melanoma have benefited overall survival rates more than chemotherapy but are limited by acquired resistance.
Researchers previously discovered the protein Wnt5A promotes metastatic progression and resistance to therapy for poorer overall prognosis, and that it is regulated by the anti-aging protein Klotho.
Their latest study found that by treating mice with a drug to promote Klotho expression, Wnt5A levels are lowered and growth of therapy-resistant melanoma is decreased in older mice -- but not young mice.
"We have already shown that age-related changes in the tumor microenvironment are accountable for the higher metastatic potential of melanoma in older patients," Ashani Weeraatna, Ph.D., Ira Brind professor, program leader of the Tumor Microenvironment and Metastasis Program at Wistar and lead author of the study, said in a press release. "Our new study indicates that a differential therapeutic approach can be beneficial for older patients in melanoma and suggests that age should be taken into account to design better treatments for certain cohorts of patients."
Researchers recreated the interactions of melanoma cells with a young or aged tumor microenvironment and found an association between Klotho, Wnt5A, melanoma cells and the tumor microenvironment.
They found they could manipulate Klotho expression pharmacologically using the anti-diabetic drug rosiglitazone, which decreased the levels of Wnt5A. The combination of rosiglitazone and targeted therapy reduced tumor growth in both young and aged models.
"We believe that there is a threshold effect whereby the levels of Klotho, dictated mostly by the age of the patients, are crucial in determining whether they will benefit from this treatment or not," Reeti Behera, Ph.D., a postdoctoral researcher and first author of the study, said in a press release. "Previous studies had tested the use of rosiglitazone for cancer treatment, but the outcome was not encouraging. I think they may have been missing a piece of the puzzle, by not considering aging and the tumor microenvironment."
The study was published in Clinical Cancer Research.