On the other hand inhibition of CAIX could be induced by upregulating ROC-1; this idea can be used as base for treating BC by causing CAIX inhibition because ROC-1 mediate un stabilization and degradation of hypoxic markers by ubiquitation of VHL as it is a component of VHL/Cullin 2/ Elongin BC/ ROC-1 complex [27]. Here, VHL is linked to breast cancer.