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Non-canonical transcriptional consequences of BET inhibition in cancer

Christopher Letson1, Eric Padron1

  • 1Moffitt Cancer Center: 12902 USF Magnolia Drive, Tampa, FL 33612, United States.

Pharmacological Research
|November 8, 2019
PubMed

Insights

Bromo and extra-terminal domain (BET) protein inhibition shows promise in preclinical cancer studies. However, clinical success is limited, and resistance necessitates exploring non-canonical effects for combination therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Bromo and extra-terminal domain (BET) proteins are crucial for cancer progression and represent significant therapeutic targets.
  • BET inhibitors induce cell cycle arrest and apoptosis by downregulating key oncogenes like MYC, CDK6, BCL2, and FOSL1.

Purpose of the Study:

  • To summarize the non-canonical consequences of BET inhibition in cancer.
  • To discuss how these non-canonical effects contribute to resistance and inform rational combination strategies.

Main Methods:

  • Literature review and synthesis of preclinical and clinical data on BET inhibitors.
  • Analysis of emerging resistance mechanisms to BET inhibition.
  • Exploration of potential combination therapies based on non-canonical BET inhibition effects.

Main Results:

  • BET inhibitors have shown limited clinical success as monotherapies.
  • Resistance to BET inhibition is increasingly reported after sustained in vitro treatment.
  • Non-canonical effects of BET inhibition, beyond direct oncogene downregulation, are being identified.

Conclusions:

  • Understanding the non-canonical consequences of BET inhibition is critical for overcoming clinical limitations.
  • Rational combination therapies targeting these non-canonical pathways could enhance the efficacy of BET inhibitors in cancer treatment.
Keywords:
BromodomainCancerNon-coding RNATranscription

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