INS and cancer: In conclusion, our research underscores (1) the repurposing of MTX, an anti-cancer drug, to address immune defects associated with Toll pathway activation; (2) the impact of the Toll and insulin pathways on developmental, hematopoietic and immune defects; and (3) the restoration of immune homeostasis in Ubc9−/− mutants through genetic rescue via Cactus overexpression, which mitigates hyperactive Toll and insulin signaling.