A genetic alteration in melanoma cells that subverts tumor suppressive mechanisms and can be targeted with available compounds to inhibit cancer growth is published online this week in Nature Medicine.
Most types of tumors carry frequent alterations that directly affect the function of p53, a crucial protector from oncogenic transformation. But traditionally, mutations in p53 are rare in melanoma, and how these cancer cells overcome p53’s suppression is not well known.
Jean-Christophe Marine and colleagues report that people with melanoma have increased levels of MDM4, a protein that can inactivate p53. Melanoma cells rely on MDM4 to overcome the tumor suppression exerted by p53 and form tumors. A previously developed peptide that disrupts the interaction between MDM4 and p53 and restores p53’s function restricts melanoma growth, suggesting that MDM4 could represent a potential therapeutic target for this deadly human cancer.