Format

Send to

Choose Destination
Sci Transl Med. 2019 Mar 20;11(484). pii: eaar5012. doi: 10.1126/scitranslmed.aar5012.

Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy.

Author information

1
Peptomyc S.L., Edifici Cellex, Hospital Vall d'Hebron, Barcelona, 08035, Spain.
2
Vall d'Hebron Institute of Oncology (VHIO), Edifici Cellex, Hospital Vall d'Hebron, Barcelona, 08035, Spain.
3
Syros Pharmaceuticals, Cambridge, MA 02139, USA.
4
Département de Biochimie, PROTÉO and Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
5
Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, 28040, Spain.
6
Peptomyc S.L., Edifici Cellex, Hospital Vall d'Hebron, Barcelona, 08035, Spain. lsoucek@vhio.net.
7
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, 08010, Spain.
8
Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, 08193 , Spain.

Abstract

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.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center