ABSTRACT We intend to devise a novel therapeutic strategy based on a specific cancer cell receptor named EphA2, which is abundant on the surface of metastatic pancreatic cancers. Over the past several years our studies focused on testing the anti-cancer potential of agents targeting the receptor in suppressing cell migration and invasion in cellular studies, as well as in inhibiting tumor metastases using in vivo models. Very recently we have derived the most effective agonistic agent reported to date that potently targets the EphA2 receptor and causes its degradation. In preliminary studies, the agent is remarkably effective in inhibiting pancreatic cancer cell migration. The agent also causes the internalization of the receptor; hence we intend to probe whether we can use this agent also to deliver chemotherapy selectively to pancreatic tumors.

PROJECT NARRATIVE We propose to target a specific tumor marker, EphA2, expressed on the surface of aggressive pancreatic cancers. We propose to develop our potent and effective EphA2 targeting agent, Targefrin, that effectively inhibits tumor metastases. We will also probe Targefrin as an effective drug deliver agent to target chemotherapy selectively to the tumor and circulating cancer cells. Hence the proposed therapeutic strategy would simultaneously eliminate the primary tumor and suppress pancreatic cancer metastases.