Drugging the "Undruggable" MYCN Oncogenic Transcription Factor: Overcoming Previous Obstacles to Impact Childhood Cancers.


Journal

Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R

Informations de publication

Date de publication:
01 04 2021
Historique:
received: 12 10 2020
revised: 28 12 2020
accepted: 22 01 2021
pubmed: 30 1 2021
medline: 12 8 2021
entrez: 29 1 2021
Statut: ppublish

Résumé

Effective treatment of pediatric solid tumors has been hampered by the predominance of currently "undruggable" driver transcription factors. Improving outcomes while decreasing the toxicity of treatment necessitates the development of novel agents that can directly inhibit or degrade these elusive targets. MYCN in pediatric neural-derived tumors, including neuroblastoma and medulloblastoma, is a paradigmatic example of this problem. Attempts to directly and specifically target MYCN have failed due to its similarity to MYC, the unstructured nature of MYC family proteins in their monomeric form, the lack of an understanding of MYCN-interacting proteins and ability to test their relevance

Identifiants

pubmed: 33509943
pii: 0008-5472.CAN-20-3108
doi: 10.1158/0008-5472.CAN-20-3108
pmc: PMC8392692
mid: NIHMS1734303
doi:

Substances chimiques

Antineoplastic Agents 0
MYCN protein, human 0
N-Myc Proto-Oncogene Protein 0

Types de publication

Historical Article Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1627-1632

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM118090
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA128583
Pays : United States

Informations de copyright

©2021 American Association for Cancer Research.

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Auteurs

Adam J Wolpaw (AJ)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Wistar Institute, Philadelphia, Pennsylvania.

Richard Bayliss (R)

Astbury Center for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom.

Gabriele Büchel (G)

Department of Biochemistry and Molecular Biology, Theodor Boveri Institute, Biocenter, University of Wuürzburg, Wuürzburg, Germany.
Mildred Scheel Early Career Center, University Hospital Wuürzburg, Wuürzburg, Germany.

Chi V Dang (CV)

Wistar Institute, Philadelphia, Pennsylvania.
Ludwig Institute for Cancer Research, New York, New York.

Martin Eilers (M)

Department of Biochemistry and Molecular Biology, Theodor Boveri Institute, Biocenter, University of Wuürzburg, Wuürzburg, Germany.

W Clay Gustafson (WC)

University of California San Francisco, UCSF Benioff Children's Hospital, San Francisco, California.

Gwenn H Hansen (GH)

Nurix Therapeutics, San Francisco, California.

Natalia Jura (N)

Cardiovascular Research Institute, University of California San Francisco, San Francisco, California.
Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California.

Stefan Knapp (S)

Institut für Pharmazeutische Chemie und Structural Genomics Consortium, Goethe-University Frankfurt, Frankfurt, Germany.

Mark A Lemmon (MA)

Department of Pharmacology and Cancer Biology Institute, Yale School of Medicine, New Haven, Connecticut.

David Levens (D)

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

John M Maris (JM)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. mosse@chop.edu maris@chop.edu.
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Ronen Marmorstein (R)

Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Steven J Metallo (SJ)

Department of Chemistry, Georgetown University, Washington, DC.

Julie R Park (JR)

Department of Pediatrics, University of Washington School of Medicine and Center for Clinical and Translational Research, Seattle Children's Hospital, Seattle, Washington.

Linda Z Penn (LZ)

Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Michael Rape (M)

Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, California.

Martine F Roussel (MF)

Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Kevan M Shokat (KM)

Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California.

William P Tansey (WP)

Vanderbilt University School of Medicine, Nashville, Tennessee.

Kliment A Verba (KA)

Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California.

Seychelle M Vos (SM)

Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.

William A Weiss (WA)

Departments of Neurology and Pediatrics, Neurological Surgery and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.

Elmar Wolf (E)

Cancer Systems Biology Group, Theodor Boveri Institute, University of Würzburg, Würzburg, Germany.

Yaël P Mossé (YP)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. mosse@chop.edu maris@chop.edu.
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

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