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Updated: Jul 15, 2026
An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
The new frontier in cancer research: deciphering cancer epigenetics
Marion Lohrum1, Hendrik G Stunnenberg, Colin Logie
1Molecular Biology Department, Nijmegen Centre for Molecular Life Sciences, Radboud University, The Netherlands.
Abstract:
Cancer has long been known to be a disease caused by alterations in the genetic blueprint of cells. In the past decade it has become apparent that epigenetic alterations also underlie the etiology of cancer. Since epigenetic changes may be more facile to reverse than genetic lesions, much research has been invested in their characterization. Success has indeed been booked in the clinic with drugs that erase DNA methylation imprints or that target histone post-translational modifications such as lysine acetylation. However, the actual consequences of current epigenetic pharmacological intervention protocols are still poorly characterized and may be rather pleiotropic in nature. The challenge we face is therefore to define the cellular enzymes responsible for epigenetic modifications at given genes under specific conditions, so as to develop pharmacological agents that target tumorigenic epigenetic lesions while eliciting minimal unwanted side effects. Application of genome-wide analytical tools has begun to provide spatio-temporally resolved data that will be crucial to achieve this goal. Finally, the molecular mode of action of epigenetic drugs may be more intricate than initially thought, involving more than DNA and histones, since it has been reported that transcription (co)factors are themselves also targeted by histone modifying enzymes.
Insights
Epigenetic alterations drive cancer development and can be targeted by drugs. Further research is needed to understand the precise mechanisms of epigenetic drugs for safer and more effective cancer treatments.
Area of Science:
- Oncology
- Epigenetics
- Pharmacology
Background:
- Cancer is a genetic disease, with epigenetic alterations also recognized as key contributors to its development.
- Epigenetic modifications, unlike genetic mutations, are potentially reversible, driving research into epigenetic therapies.
- Current epigenetic drugs show clinical success but their broad effects and precise mechanisms remain incompletely understood.
Purpose of the Study:
- To define the specific enzymes responsible for epigenetic modifications in cancer.
- To develop targeted epigenetic drugs with minimal side effects.
- To elucidate the complex molecular mechanisms of epigenetic drug action.
Main Methods:
- Utilizing genome-wide analytical tools to generate spatio-temporally resolved epigenetic data.
- Characterizing the role of DNA methylation and histone post-translational modifications in cancer.
- Investigating the involvement of transcription factors and cofactors in epigenetic drug responses.
Main Results:
- Epigenetic drugs targeting DNA methylation and histone acetylation have shown promise in clinical settings.
- The consequences of current epigenetic interventions are pleiotropic and require further characterization.
- Emerging evidence suggests transcription (co)factors are also targets of epigenetic modifying enzymes.
Conclusions:
- Understanding the specific enzymes driving epigenetic lesions is crucial for developing precise cancer therapies.
- Genome-wide data is essential for mapping epigenetic modifications and guiding drug development.
- The molecular targets of epigenetic drugs may extend beyond DNA and histones, necessitating a broader investigation.
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