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Beaulieu, Marie-Eve; Jauset, Toni; Massó-Vallés, Daniel; Martínez-Martín, Sandra; Rahl, Peter; Maltais, Loïka; Zacarias-Fluck, Mariano F; Casacuberta-Serra, Sílvia; Serrano Del Pozo, Erika; Fiore, Christopher; Foradada, Laia; Cano, Virginia Castillo; Sánchez-Hervás, Meritxell; Guenther, Matthew; Romero Sanz, Eduardo; Oteo, Marta; Tremblay, Cynthia; Martín, Génesis; Letourneau, Danny; Montagne, Martin; Morcillo Alonso, Miguel Ángel; Whitfield, Jonathan R; Lavigne, Pierre; Soucek, Laura
Science translational medicine, 03/2019, Letnik: 11, Številka: 484Journal Article
Inhibiting MYC has long been considered unfeasible, although its key role in human cancers makes it a desirable target for therapeutic intervention. One reason for its perceived undruggability was the fear of catastrophic side effects in normal tissues. However, we previously designed a dominant-negative form of MYC called Omomyc and used its conditional transgenic expression to inhibit MYC function both in vitro and in vivo. MYC inhibition by Omomyc exerted a potent therapeutic impact in various mouse models of cancer, causing only mild, well-tolerated, and reversible side effects. Nevertheless, Omomyc has been so far considered only a proof of principle. In contrast with that preconceived notion, here, we show that the purified Omomyc mini-protein itself spontaneously penetrates into cancer cells and effectively interferes with MYC transcriptional activity therein. Efficacy of the Omomyc mini-protein in various experimental models of non-small cell lung cancer harboring different oncogenic mutation profiles establishes its therapeutic potential after both direct tissue delivery and systemic administration, providing evidence that the Omomyc mini-protein is an effective MYC inhibitor worthy of clinical development.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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