The JM1-24-3 full-length mAb and F (ab’)2 treatment RPPA data together with IPA analysis revealed that JM1-24-3 binding to MUC18 initiated signaling in fundamentally important canonical cancer pathways, including PI3K/AKT and neuregulin; the top associated upstream regulators were TP53, MYC, ESR1 and others; the most important molecular and cellular functions impacted were those associated with cell death and survival, cellular development, and cellular growth and proliferation (Supplementary Fig. S3A). The gene discussed is ESR1; the disease is cancer.