Reported mechanisms include overexpression or mutations in PSMB5 (the proteasomal target of BTZ), P-glycoprotein expression (efflux pump), microenvironmental upregulation of IL-6, IGF-1, or tumor upregulation of HSP90, PI3K, MYC, and IGF-1 [8, 32-36]. The gene discussed is IGF1; the disease is neoplasm.