Despite recent progress in surgical procedures and therapeutic modalities, the outcomes of treatment for pancreas cancer are still not satisfactory. Chemotherapy can provide symptom relief in some patients, but its impact on survival has been modest and it can lead to unacceptable levels of toxicity. To develop novel and potentially less toxic forms of cancer therapy, molecular targeting therapy is being based initially on the knowledge of cellular signal transduction. The new approaches in treatment have originated from biochemical studies in combination with recent technology to block the progress of carcinogenesis or invasion. As one of the most successful of such agents, an antibody or antagonist against the receptor of epidermal growth factor or vascular endothelial growth factor has been proven in carcinoma treatment, and recent steps have been taken to apply this type of treatment to pancreas cancer. However, there are still serious problems for these receptor-associated signaling blockers; namely, the antibody or antagonist has no efficacy if the target cells grow independently of the receptor-related signaling. On the other hands, extra-cellular signal-regulated kinase (ERK) is well known to represent a convergent point for the intracellular signaling pathways in whole cancer cells. In the present, by reviewing our recent studies that evaluate the usefulness of the vitamin K3 (menadione, 2-methyl-1,4-naphthoquinone; VK3)-induced growth inhibitory effect through ERK pathway, this novel approach to cancer therapy and its potential in future clinical applications will be highlighted.