Kikuchi et al. demonstrated that pharmacological and genetic inhibition of the IGF1R-PI3K-AKT pathway reverses CAM-DR by promoting enhancer of zeste homolog 2 (EZH2) dephosphorylation and H3K27 hypermethylation both in vitro and in refractory murine MM models, suggesting an epigenetic mechanism underlying CAM-DR [130]. This evidence concerns the gene EZH2 and Miyoshi myopathy.