We went on to characterize the molecular events underlying the anti-MM response to LTI6426/Pano, which induces synergistic transcriptional upregulation of key effectors in the ER stress pathway including ATF3, DDIT3/CHOP, and DNAJB1. We extended our findings to test LTI6426 with Pano in vivo using a mouse model of treatment resistant MM in a multidrug cocktail that also includes Btz, which is representative of the FDA-approved regimen for Pano in relapsed/refractory MM. Here, CASC3 is linked to Miyoshi myopathy.