Thus collectively our data from previous work and the present studies argue that by modulating the function of the chaperones GRP78 and HSP27, regardless of the many other chaperones we also now know are effected by [sorafenib/regorafenib + sildenafil] exposure; it promotes toxic autophagosome formation through two distinct mechanisms and thus this is why the catabolic process is associated with [sorafenib/regorafenib + sildenafil] –induced tumor cell death rather than survival. The gene discussed is HSPA5; the disease is neoplasm.