Invasive breast cancers express PKD2 and PKD3, but not PKD1. Two strategies have been shown to be successful in preclinical animal models. First, PKD1 re-expression can be initiated by treatment with DNA methyltransferase inhibitors (DMTIs). Upregulation of PKD1 bocks invasion and metastasis, and additional activation with activators such as suramin further enhances these effects. A second strategy is the use of pan PKD inhibitors to target oncogenic functions of PKD2 and PKD3. Inhibition of PKD3 decreases tumor cell proliferation, invasion and metastasis. Inhibition of PKD2 in cancer cell lines has been shown to decrease multidrug resistance, and therefore it is predicted that PKD inhibitors will act synergistically with currently-used conventional chemotherapy, by sensitizing cancer cells to these agents.