Towards a more precise therapy in cancer: Exploring epigenetic complexity

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.