Research ArticleCancer

A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent

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Science Translational Medicine  23 May 2018:
Vol. 10, Issue 442, eaah4807
DOI: 10.1126/scitranslmed.aah4807

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Semaphoring to tumor vasculature

Solid tumors typically have blood vessels that are not only increased in number but also exhibit various structural and functional abnormalities. Thus, vascular normalization is frequently proposed as an antitumor strategy, with the goal of improving intratumoral oxygenation and drug delivery. SEMA3A, a protein from the semaphorin family, is a known vascular normalizing agent but not a good therapeutic candidate due to adverse effects. To address this concern, Gioelli et al. engineered a mutant version of SEMA3A that retained its vascular normalizing function but did not activate the pathway responsible for the main side effects. The authors then confirmed the ability of mutant SEMA3A to normalize tumor vasculature and demonstrated its anticancer effects alone and combined with chemotherapy.