Related Experiment Video
Updated: Feb 24, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
7.0K
BET inhibitors: a novel epigenetic approach
D B Doroshow1, J P Eder1, P M LoRusso1
1Section of Medical Oncology, Department of Medicine, Yale University and Yale Cancer Center, New Haven, USA.
Summary
Bromodomain and extra-terminal motif (BET) inhibitors show promise in epigenetic cancer therapy, but limited efficacy as single agents. Combination therapies, particularly with histone deacetylase (HDAC) inhibitors, may enhance outcomes and reduce toxicity.
Area of Science:
- Epigenetics and cancer therapeutics
- Molecular mechanisms of gene regulation
- Pharmacology of novel anticancer agents
Background:
- Epigenetic drugs, including BET protein inhibitors, are emerging anticancer agents.
- BET proteins regulate transcription and cell cycle, making them targets for cancer therapy.
- BET inhibitors selectively target tumor cells by binding to superenhancers, crucial for gene transcription.
Purpose of the Study:
- To review the role of BET inhibitors in epigenetic cancer therapy.
- To evaluate the clinical efficacy and toxicities of BET inhibitors.
- To explore the potential of BET inhibitors in combination therapies.
Main Methods:
- Review of preclinical and early clinical trial data on BET inhibitors.
- Analysis of BET inhibitor mechanisms, including MYC targeting and superenhancer binding.
- Examination of synergistic effects with other anticancer agents, including HDAC inhibitors and immune checkpoint inhibitors.
Main Results:
- Early clinical trials of BET inhibitors showed limited and short-lived responses in hematologic and solid tumors.
- Common toxicities included thrombocytopenia, fatigue, nausea, and gastrointestinal side-effects.
- Preclinical data indicate strong synergy between BET inhibitors and other epigenetic agents, especially HDAC inhibitors, at reduced doses.
Conclusions:
- BET inhibitors represent a novel approach to epigenetic anticancer therapy but have limited monotherapy efficacy.
- Combination strategies involving BET inhibitors with targeted agents, immune checkpoint inhibitors, or other epigenetic agents are warranted.
- Further research focusing on combination therapies may overcome resistance and improve outcomes while mitigating overlapping toxicities.
More Related Videos
Related Concept Videos
01:52Eukaryotic Transcription Inhibitors
11.1K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.1K
01:46Epigenetic Regulation
34.0K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
34.0K
01:37Epigenetic Regulation
4.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
4.0K
01:30Enzyme Inhibition
93.2K
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
93.2K
01:29Pharmacogenomics: Identification of New Drug Targets
29
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
29
02:30Genomic Imprinting and Inheritance
37.6K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
37.6K