Targeting the ERK-MAP kinase pathway in cancer therapy

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Specific blockade of the ERK pathway by MEK inhibitors alone induces mostly cytostatic rather than pro-apoptotic effects, resulting in a limited therapeutic efficacy of MEK inhibitors. However, MEK inhibitors specifically and markedly sensitize various humor tumor xenografts to microtubule-destabilizing agent-/HDAC inhibitor-induced cytotoxicity. Our results clearly indicate that administration of both a MEK inhibitor and a microtubule-destabilizing agent/HDAC inhibitor represents a promising chemotherapeutic strategy with improved safety for cancer patients.