Metastatic uveal melanomas are highly resistant to all existing treatments. Here, a kinome-wide CRISPR-Cas9 knockout screen, revealed that the LKB1-SIK2 module plays a critical role in constraining uveal melanoma cell tumorigenesis. The inventors’ results demonstrate that a combination of SLC8A1 inhibitor and mitochondria-targeted antioxidant has an enhanced cell death efficacy in LKB1 and SIK2-negative uveal melanoma cells. They also designed a LKB1 loss gene signature that is predictive of patient survival and treatment response. Their data thus identify new prognosis markers, and metabolic vulnerability, thereby providing a therapeutic
strategy for these subtypes of metastatic uveal melanomas.
The present invention relates to a method for treating melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of a combination of SLC8A1 inhibitor and mitochondria-targeted antioxidant.