Genetic mutations and inhibitors of p300 and CBP

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• p300 and CBP are highly homologous enzymes implicated in cancer progression.
• Inhibitors targeting the catalytic domain (HAT) or bromodomain (BRD) have been developed.
• Despite promising preclinical data, clinical approval for p300/CBP inhibitors is lacking.

Purpose of the Study:

• To review mutations in EP300 and CREBBP genes.
• To analyze the frequency and potential impact of these mutations.
• To discuss how genetic alterations influence the efficacy of pharmacological agents targeting p300/CBP.

Main Methods:

• Literature review of EP300 and CREBBP mutations.
• Analysis of mutation frequency and functional impact.
• Discussion of genotype-phenotype correlations in cancer treatment.

Main Results:

• EP300 and CREBBP mutations are observed in various cancers.
• Specific mutations in HAT and BRD domains may affect drug binding and efficacy.
• Understanding these mutations is crucial for personalized cancer therapy.

Conclusions:

• Mutations in EP300 and CREBBP present challenges and opportunities for p300/CBP targeted cancer therapy.
• Further research into genotype-specific responses to inhibitors is warranted.
• This review provides a framework for evaluating the clinical utility of p300/CBP inhibitors based on patient genetic profiles.