MC1R and metastatic melanoma: Upregulation of DNA repair pathways in melanoma has been linked with metastasis and poor patient prognosis, which may be attributed to their ability to avoid catastrophic levels of DNA damage.39 It’s also not surprising to note that carrying certain MC1R variant alleles may confer a significantly increased risk of melanoma progression.40 Although most primary and metastatic melanoma specimens in our cohort had elevated MC1R expression, there remains a subset of samples with relatively low levels, and these patients might have poor response to MC1R-targeting therapies.