MAP3K8 and cancer: XL888 has shown significant activity in overcoming resistance to BRAF (B-Raf proto-oncogene, serine/threonine kinase) inhibitors in melanoma models by degrading multiple resistance mediators such as platelet derived growth factor receptor beta (PDGFRβ), COT (Cancer Osaka Thyroid/MAP3K8), and insulin-like growth factor 1 receptor (IGF1R), thereby restoring apoptosis and enhancing the efficacy of BRAF-targeted therapies[115].