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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2015

Examination of HER3 targeting in cancer using monoclonal antibodies

Lucile Mounier
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Résumé

The human EGF receptor (HER/EGFR) family of receptor tyrosine kinases serves as a key target for cancer therapy. Specifically, EGFR and HER2 have been repeatedly targeted because of their genetic aberrations in tumors. The therapeutic potential of targeting HER3 has long been underestimated, due to relatively low expression in tumors and impaired kinase activity. Nevertheless, in addition to serving as a dimerization partner of EGFR and HER2, HER3 acts as a key player in tumor cells' ability to acquire resistance to cancer drugs. In this study, we generated several monoclonal antibodies to HER3. Comparisons of their ability to degrade HER3, decrease downstream signaling, and inhibit growth of cultured cells, as well as recruit immune effector cells, selected an antibody that later emerged as the most potent inhibitor of pancreatic cancer cells grown as tumors in animals. Our data predict that anti-HER3 antibodies able to intercept autocrine and stroma-tumor interactions might strongly inhibit tumor growth, in analogy to the mechanism of action of anti-EGFR antibodies routinely used now to treat colorectal cancer patients.

Domaines

Cancer
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Dates et versions

hal-02276327 , version 1 (02-09-2019)

Licence

Paternité - Pas d'utilisation commerciale

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Nadège Gaborit, Ali Abdul-Hai, Maicol Mancini, Moshit Lindzen, Sara Lavi, et al.. Examination of HER3 targeting in cancer using monoclonal antibodies. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112 (3), pp.839-844. ⟨10.1073/pnas.1423645112⟩. ⟨hal-02276327⟩
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