Imatinib Inhibits EphB Abl Signaling Pathway and Suppresses Colorectal Cancer

Imatinib Inhibits EphB Abl Signaling Pathway and Suppresses Colorectal Cancer

shutterstock_210988051Researchers from Karolinska Institutet in Sweden and Nanyang Technological University in Singapore showed that the drug Imatinib, a tyrosine kinase inhibitor used in leukemia, can inhibit the development of intestinal tumors. The study entitled “Na EphB Abl signaling pathway is associated with intestinal tumor initiation and growth” was published in the journal Science Translational Medicine by Parag Kundu and Maria Genander, co-first authors, Jonas Frisén and Sven Pettersson, co-seniors authors, and colleagues.

The research team showed that Imatinib can suppress the development of adenoma in the intestine by targeting the EphB-signaling pathway. Ephrin type-B (EphB) receptors regulate the proliferation and positioning of intestinal stem and progenitor cells. Moreover, they promote the development of adenoma but inhibit its progress into invasive carcinoma.

Researchers used genetically engineered mice susceptible to intestinal adenomas with different levels of severity, treated them with Imatinib and compared with untreated controls. They observed that Imatinib inhibited adenoma at the stem cell level by 50%, which significantly reduced tumor development. To confirm their findings, researchers used human colonic tumor explants from patients, observing promising long term effects, as Imatinib increased the life span of a mouse model that mimics human colon cancer. Surprisingly, the drug was also successful in increasing the survival of mice with late-stage adenomas and rectal bleeding.

These results suggest that the use of chemotherapies for short periods could be an alternative therapy strategy to reduce the adverse effects induced by Imantinib during longer treatment periods.

Professor Jonas Frisén at Stem Cell Research at Karolinska Institutet stated these results show Imatinib therapy does not affect the tumor suppressor function of EphB receptors.

Professor Sven Pettersson, from Karolinska Institutet and Lee Kong Chain School of Medicine at Nanyang Technological University, added hat their study may have a relevant clinical impact since Imatinib is a potential new drug for the therapy of adenoma formation and cancer development in patients susceptible to develop colorectal cancer.

These new data could become relevant for the development of novel therapies to inhibit adenoma formation and cancer progression in patients susceptible to colorectal cancer.

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