Receptors of the EphB family regulate the proliferation and positioning of intestinal stem and progenitor cells. Although these receptors act as tumor promoters for adenoma development, EphB suppresses progression to invasive carcinoma. Using a mouse model of familial adenomatous polyposis (FAP), Kundu et al. present evidence that imatinib, an inhibitor of the kinase Abl, specifically abrogates the tumor-promoting effect of EphB without affecting the tumor-suppressor functions, thereby prolonging the life span of these mice. Imatinib also reduced cell proliferation in cultured slices of adenomas from FAP patients, suggesting that this treatment might be a possibility for patients with FAP who are predisposed to develop colon cancer.
P. Kundu, M. Genander, K. Strååt, J. Classon, R. A. Ridgway, E. H. Tan, J. Björk, A. Martling, J. van Es, O. J. Sansom, H. Clevers, S. Pettersson, J. Frisén, An EphB-Abl signaling pathway is associated with intestinal tumor initiation and growth. Sci. Transl. Med. 7, 281ra44 (2015). [Abstract]