Drug Discovery and Chemical Biology of Cancer Epigenetics

Area of Science:

• Oncology
• Epigenetics
• Genomics

Background:

• Comprehensive genomic and transcriptomic analyses reveal widespread mutations in chromatin-modifying proteins (CMPs) across diverse cancers.
• Epigenetic dysregulation, driven by CMP mutations, is a common hallmark of both pediatric and adult malignancies.

Purpose of the Study:

• To review genetic mutations in epigenetic genes.
• To summarize chromatin-modifying protein (CMP) inhibitors relevant for preclinical and clinical cancer studies.
• To identify CMPs lacking potent inhibitors, guiding future research efforts.

Main Methods:

• Review of existing literature on genetic mutations in epigenetic genes.
• Compilation of data on chromatin-modifying protein (CMP) inhibitors currently in preclinical or clinical development.
• Analysis of CMPs with identified mutations but lacking targeted inhibitors.

Main Results:

• Genetic mutations in epigenetic genes, particularly CMPs, are prevalent in various cancer types.
• Numerous potent inhibitors targeting various CMP classes have been developed, aiding the study of epigenetic roles and vulnerabilities.
• Several CMPs with significant roles in cancer lack developed inhibitors, indicating areas for future therapeutic development.

Conclusions:

• Epigenetic dysregulation is a critical factor in cancer development and progression.
• Targeted inhibition of CMPs represents a promising therapeutic strategy for a wide range of cancers.
• Further research into novel CMP inhibitors is warranted to address unmet clinical needs in epigenetic cancer therapy.