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Updated: Nov 24, 2025
An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
Targeting Chromatin Complexes in Myeloid Malignancies and Beyond: From Basic Mechanisms to Clinical Innovation
Florian Perner1,2, Scott A Armstrong1
1Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Abstract:
The aberrant function of chromatin regulatory networks (epigenetics) is a hallmark of cancer promoting oncogenic gene expression. A growing body of evidence suggests that the disruption of specific chromatin-associated protein complexes has therapeutic potential in malignant conditions, particularly those that are driven by aberrant chromatin modifiers. Of note, a number of enzymatic inhibitors that block the catalytic function of histone modifying enzymes have been established and entered clinical trials. Unfortunately, many of these molecules do not have potent single-agent activity. One potential explanation for this phenomenon is the fact that those drugs do not profoundly disrupt the integrity of the aberrant network of multiprotein complexes on chromatin. Recent advances in drug development have led to the establishment of novel inhibitors of protein-protein interactions as well as targeted protein degraders that may provide inroads to longstanding effort to physically disrupt oncogenic multiprotein complexes on chromatin. In this review, we summarize some of the current concepts on the role epigenetic modifiers in malignant chromatin states with a specific focus on myeloid malignancies and recent advances in early-phase clinical trials.
Insights
Aberrant epigenetic regulation drives cancer. Novel protein-protein interaction inhibitors and targeted protein degraders offer new strategies to disrupt cancer-promoting chromatin complexes, especially in myeloid malignancies.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Aberrant epigenetic regulation is a key driver of cancer, promoting oncogenic gene expression.
- Disrupting chromatin-associated protein complexes shows therapeutic potential in malignancies.
- Current histone modifying enzyme inhibitors often lack potent single-agent activity due to incomplete network disruption.
Purpose of the Study:
- To review the role of epigenetic modifiers in malignant chromatin states.
- To focus on myeloid malignancies and their specific epigenetic alterations.
- To summarize recent advances in early-phase clinical trials for epigenetic therapies.
Main Methods:
- Review of current literature on epigenetics in cancer.
- Analysis of therapeutic strategies targeting chromatin regulatory networks.
- Focus on novel inhibitors of protein-protein interactions and targeted protein degraders.
- Examination of clinical trial data for epigenetic therapies in myeloid malignancies.
Main Results:
- Epigenetic modifiers play a crucial role in establishing and maintaining malignant chromatin states.
- Novel therapeutic approaches targeting protein-protein interactions and protein degradation are emerging.
- Early-phase clinical trials show promise for these new strategies, particularly in myeloid cancers.
Conclusions:
- Targeting multiprotein complexes involved in aberrant epigenetics is a promising therapeutic avenue.
- Novel drug development strategies are needed to overcome limitations of existing epigenetic therapies.
- Further research and clinical trials are essential to fully realize the potential of these new approaches in treating myeloid malignancies.
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