Study: Potential therapeutic target identified to treat melanoma

Source: UAB News, September 2022

Melanoma is a highly aggressive skin cancer that frequently metastasizes, but current therapies benefit only some patients. Finding new ways to treat melanoma and other cancers is crucial because of the high prevalence of acquired resistance to currently used therapy for treating patients.

University of Alabama at Birmingham researcher Romi Gupta, Ph.D., assistant professor of biochemistry and molecular genetics, and colleagues found that CDC7, which is a highly conserved cell-cycle regulator with an important role in DNA replication, is overexpressed in melanoma, and patients with higher expression have shorter survival. Their work further revealed that CDC7 promotes melanoma tumor growth, and its inhibition blocks melanoma growth by promoting cell cycle arrest, senescence and apoptosis.

Gupta and colleagues further used a chemical genetics screen with epigenetic inhibitors that revealed stronger melanoma tumor growth inhibition when CDC7 inhibitor XL413 is combined with the EZH2 inhibitor GSK343 or BRPF1/2/3 inhibitor OF1. Mechanistically, they found that XL413 in combination with GSK343 or OF1 synergistically alters the expression of several tumor-suppressive genes, leading to higher apoptosis than the single agent alone. These findings suggested that the administration of XL413 in combination with GSK343 or OF1 could be a superior therapeutic approach for melanoma.

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