The Molecular 'Myc-anisms' Behind Myc-Driven Tumorigenesis and the Relevant Myc-Directed Therapeutics

Int J Mol Sci. 2020 Dec 13;21(24):9486. doi: 10.3390/ijms21249486.

Abstract

MYC, a well-studied proto-oncogene that is overexpressed in >20% of tumors across all cancers, is classically known as "undruggable" due to its crucial roles in cell processes and its lack of a drug binding pocket. Four decades of research and creativity led to the discovery of a myriad of indirect (and now some direct!) therapeutic strategies targeting Myc. This review explores the various mechanisms in which Myc promotes cancer and highlights five key therapeutic approaches to disrupt Myc, including transcription, Myc-Max dimerization, protein stability, cell cycle regulation, and metabolism, in order to develop more specific Myc-directed therapies.

Keywords: cancer; cell cycle; inhibitors; max; metabolism; myc; stability; synthetic lethality; transcription.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Cell Cycle / drug effects*
  • Dimerization
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Protein Stability / drug effects
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Synthetic Lethal Mutations / genetics
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MAS1 protein, human
  • MAX protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc