Taking the Myc out of Cancer: Toward Therapeutic Strategies to Directly Inhibit c-Myc

Sarah Madden; Aline Dantas de Araujo; Mara Gerhardt; David Fairlie; Jody Mason

doi:10.1186/s12943-020-01291-6

Taking the Myc out of Cancer: Toward Therapeutic Strategies to Directly Inhibit c-Myc

Sarah Madden, Aline Dantas de Araujo, Mara Gerhardt, David Fairlie, Jody Mason

Research output: Contribution to journal › Review article › peer-review

305 Citations (SciVal)

Abstract

c-Myc is a transcription factor that is constitutively and aberrantly expressed in over 70% of human cancers. Its direct inhibition has been shown to trigger rapid tumor regression in mice with only mild and fully reversible side effects, suggesting this to be a viable therapeutic strategy. Here we reassess the challenges of directly targeting c-Myc, evaluate lessons learned from current inhibitors, and explore how future strategies such as miniaturisation of Omomyc and targeting E-box binding could facilitate translation of c-Myc inhibitors into the clinic.

Original language	English
Article number	3
Journal	Molecular Cancer
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12943-020-01291-6
Publication status	Published - 4 Jan 2021

Funding

JMM is grateful to Cancer Research UK (A26941). JMM and DPF also wish to thank the Medical Research Council (MRC) (MR/T028254/1) and the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R017956/1, BB/T018275/1). DPF thanks the National Health and Medical Research Council of Australia (NHMRC) for a Senior Principal Research Fellowship (1117017) and the Australian Research Council for grant support (CE140100011).

Keywords

Leucine zipper
Oncogene
Peptide
Protein-protein interaction
Transcription

ASJC Scopus subject areas

Molecular Medicine
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s12943-020-01291-6Licence: CC BY

Cite this

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title = "Taking the Myc out of Cancer: Toward Therapeutic Strategies to Directly Inhibit c-Myc",

abstract = "c-Myc is a transcription factor that is constitutively and aberrantly expressed in over 70\% of human cancers. Its direct inhibition has been shown to trigger rapid tumor regression in mice with only mild and fully reversible side effects, suggesting this to be a viable therapeutic strategy. Here we reassess the challenges of directly targeting c-Myc, evaluate lessons learned from current inhibitors, and explore how future strategies such as miniaturisation of Omomyc and targeting E-box binding could facilitate translation of c-Myc inhibitors into the clinic.",

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T1 - Taking the Myc out of Cancer

T2 - Toward Therapeutic Strategies to Directly Inhibit c-Myc

AU - Madden, Sarah

AU - Dantas de Araujo, Aline

AU - Gerhardt, Mara

AU - Fairlie, David

AU - Mason, Jody

PY - 2021/1/4

Y1 - 2021/1/4

N2 - c-Myc is a transcription factor that is constitutively and aberrantly expressed in over 70% of human cancers. Its direct inhibition has been shown to trigger rapid tumor regression in mice with only mild and fully reversible side effects, suggesting this to be a viable therapeutic strategy. Here we reassess the challenges of directly targeting c-Myc, evaluate lessons learned from current inhibitors, and explore how future strategies such as miniaturisation of Omomyc and targeting E-box binding could facilitate translation of c-Myc inhibitors into the clinic.

AB - c-Myc is a transcription factor that is constitutively and aberrantly expressed in over 70% of human cancers. Its direct inhibition has been shown to trigger rapid tumor regression in mice with only mild and fully reversible side effects, suggesting this to be a viable therapeutic strategy. Here we reassess the challenges of directly targeting c-Myc, evaluate lessons learned from current inhibitors, and explore how future strategies such as miniaturisation of Omomyc and targeting E-box binding could facilitate translation of c-Myc inhibitors into the clinic.

KW - Leucine zipper

KW - Oncogene

KW - Peptide

KW - Protein-protein interaction

KW - Transcription

UR - https://www.scopus.com/pages/publications/85098621900

U2 - 10.1186/s12943-020-01291-6

DO - 10.1186/s12943-020-01291-6

M3 - Review article

SN - 1476-4598

VL - 20

JO - Molecular Cancer

JF - Molecular Cancer

IS - 1

M1 - 3

ER -

Taking the Myc out of Cancer: Toward Therapeutic Strategies to Directly Inhibit c-Myc

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

From Peptides to Mimetics: Towards Smaller More Stable Drug-like Protein-protein Interaction Inhibitors

Irreversibly Silencing Oncogenic Master-regulator cMyc Using Library-derived Electrophilic Helical Peptides

A Generalised Approach to Derive Functionally Active Peptide Inhibitors of Transcription Factor Activity

Cite this

Taking the Myc out of Cancer: Toward Therapeutic Strategies to Directly Inhibit c-Myc

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

From Peptides to Mimetics: Towards Smaller More Stable Drug-like Protein-protein Interaction Inhibitors

Irreversibly Silencing Oncogenic Master-regulator cMyc Using Library-derived Electrophilic Helical Peptides

A Generalised Approach to Derive Functionally Active Peptide Inhibitors of Transcription Factor Activity

Cite this