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Towards a more precise therapy in cancer: Exploring epigenetic complexity.

Fernando P Cossío1, Manel Esteller2, María Berdasco3

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Summary

Targeting epigenetic dysregulation with epidrugs shows promise for treating diseases. This review explores strategies for developing novel epidrugs, including dual hybrids and combination therapies, to improve cancer treatment outcomes.

Keywords:
ChemoresistanceDNA methylationDual inhibitorsEpidrugsHistone modificationsImmunotherapyMultitargetingSynthetic lethality

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Area of Science:

  • Chemical biology
  • Pharmacology
  • Oncology

Background:

  • Preclinical evidence supports targeting epigenetic dysregulation as a potent strategy for human diseases.
  • Clinical application of epigenetic drugs (epidrugs) is limited, primarily to hematological malignancies.

Purpose of the Study:

  • To discuss advanced strategies for the chemical design, biological rationale, and clinical trial development of epidrugs.
  • To explore novel approaches for enhancing the efficacy of epidrugs in cancer treatment.

Main Methods:

  • Focus on developing dual hybrids for multitargeting of key epigenetic molecules in cancer.
  • Investigating epigenetic-synthetic lethality interactions to address loss-of-function mutations.
  • Examining combinations of epidrugs with other therapies, such as immunotherapy, to overcome chemoresistance and enhance sensitivity.

Main Results:

  • Strategies discussed aim to increase the clinical benefit of epigenetic chemical biology.
  • Development of more effective epidrugs targeting the aberrant epigenome in both hematological and solid tumors is anticipated.

Conclusions:

  • Novel strategies in chemical design, biological rationale, and clinical development are crucial for advancing epidrugs.
  • Combination therapies and multitargeting approaches hold significant potential for improving cancer treatment efficacy and overcoming resistance.