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Whitfield JR, Beaulieu ME, Soucek L. Strategies to Inhibit Myc and Their Clinical Applicability. Front Cell Dev Biol. 2017;5:10doi: 10.3389/fcell.2017.00010.
Whitfield, J. R., Beaulieu, M. E., & Soucek, L. (2017). Strategies to Inhibit Myc and Their Clinical Applicability. Frontiers in cell and developmental biology, 510. https://doi.org/10.3389/fcell.2017.00010
Whitfield, Jonathan R, et al. "Strategies to Inhibit Myc and Their Clinical Applicability." Frontiers in cell and developmental biology vol. 5 (2017): 10. doi: https://doi.org/10.3389/fcell.2017.00010
Whitfield JR, Beaulieu ME, Soucek L. Strategies to Inhibit Myc and Their Clinical Applicability. Front Cell Dev Biol. 2017 Feb 23;5:10. doi: 10.3389/fcell.2017.00010. eCollection 2017. PMID: 28280720; PMCID: PMC5322154.
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Front Cell Dev Biol. 2017 Feb 23;5:10. doi: 10.3389/fcell.2017.00010. eCollection 2017.

Strategies to Inhibit Myc and Their Clinical Applicability.

Frontiers in cell and developmental biology

Jonathan R Whitfield, Marie-Eve Beaulieu, Laura Soucek

Affiliations

  1. Vall d'Hebron Institute of Oncology, Edifici Cellex, Hospital Vall d'Hebron Barcelona, Spain.
  2. Peptomyc, Edifici Cellex, Hospital Vall d'Hebron Barcelona, Spain.
  3. Vall d'Hebron Institute of Oncology, Edifici Cellex, Hospital Vall d'HebronBarcelona, Spain; Peptomyc, Edifici Cellex, Hospital Vall d'HebronBarcelona, Spain; Institució Catalana de Recerca i Estudis AvançatsBarcelona, Spain; Department of Biochemistry and Molecular Biology, Universitat Autònoma de BarcelonaBellaterra, Spain.

PMID: 28280720 PMCID: PMC5322154 DOI: 10.3389/fcell.2017.00010

Abstract

Myc is an oncogene deregulated in most-perhaps all-human cancers. Each Myc family member, c-, L-, and N-Myc, has been connected to tumor progression and maintenance. Myc is recognized as a "most wanted" target for cancer therapy, but has for many years been considered undruggable, mainly due to its nuclear localization, lack of a defined ligand binding site, and physiological function essential to the maintenance of normal tissues. The challenge of identifying a pharmacophore capable of overcoming these hurdles is reflected in the current absence of a clinically-viable Myc inhibitor. The first attempts to inhibit Myc used antisense technology some three decades ago, followed by small molecule inhibitors discovered through "classical" compound library screens. Notable breakthroughs proving the feasibility of systemic Myc inhibition were made with the Myc dominant negative mutant Omomyc, showing both the great promise in targeting this infamous oncogene for cancer treatment as well as allaying fears about the deleterious side effects that Myc inhibition might have on normal proliferating tissues. During this time many other strategies have appeared in an attempt to drug the undruggable, including direct and indirect targeting, knockdown, protein/protein and DNA interaction inhibitors, and translation and expression regulation. The inhibitors range from traditional small molecules to natural chemicals, to RNA and antisense, to peptides and miniproteins. Here, we briefly describe the many approaches taken so far, with a particular focus on their potential clinical applicability.

Keywords: Myc; Omomyc; clinical application; inhibitor; oncogene; therapy

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