Semaphorin 3D and Plexin D1 as New Therapeutic Targets for Pancreatic Cancer Treatment

Unmet Need: Most patients with pancreatic ductal adenocarcinoma (PDA) present with metastatic disease at the time of diagnosis or will recur with metastases after surgical treatment.
Technology Overview: Semaphorin-plexin signaling mediates the migration of neuronal axons during development and of blood vessels during angiogenesis. The expression of the gene encoding semaphorin 3D (Sema3D) is increased in PDA tumors. Sema3D from PDA cells coimmunoprecipitated with the co-receptor plexin D1 (PlxnD1) on PDA cells. Mouse PDA cells in which SEMA3D was knocked down exhibited decreased invasive and metastatic potential in culture and in mice. Thus, plexin D1 and Sema3D may be new therapeutic targets and prognostic markers of metastatic PDA.
Stage of Development: Patients with primary PDA tumors that have abundant Sema3D have widely metastatic disease and decreased survival compared to patients with tumors that have relatively low Sema3D abundance. The secretion of Sema3D subsequently activates PlxnD1. Immunohistochemistry studies linking the increase in abundance of Sema3D and PlxnD1 in human PDA metastasis with poorer survival, provide evidence suggesting that they are important for human PDA metastasis development.
Publications:
https://www.ncbi.nlm.nih.gov/pubmed/26243191
 
 

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