Awakening the Giant — p53 Reactivation Potentiates Melanoma Therapy

Restoring TP53 tumor-suppressive signaling via HDM2 inhibition to suppress melanoma growth

The well-established sensitivity of BRAF mutant melanomas to BRAF or MEK kinase inhibitors has led to promising therapies for melanoma. Although the TP53 tumor-suppressor gene is mutated in many human cancers, it is often normal in melanoma. It has been assumed that TP53, though present, is functionally compromised — principally through the deletion of the upstream regulator p14ARF, which is often lost in the context of CDKN2A deletion. p53 activity is regulated by its transcriptional target HDM2, which binds p53, shuttling it out of the nucleus and targeting it for destruction.

Using the small molecule inhibitor nutlin-3, Ji and colleagues explored the consequences of interrupting p53–HDM2 binding in melanoma cell lines. In melanomas with n…

Reviewing Author

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology

Awakening the Giant — p53 Reactivation Potentiates Melanoma Therapy

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Reviewing Author