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Direct Measurement of KDM1A Target Engagement Using Chemoprobe-based Immunoassays
Published on: June 13, 2019
Current advances and future directions in targeting histone demethylases for cancer therapy
June-Ha Shin1, Hye-Been Yoo1, Jae-Seok Roe1
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Abstract:
Epigenetic regulators, known as "writers," erasers," and "readers," are essential for controlling gene expression by adding, removing, or recognizing post-translational modifications to histone tails, respectively. These regulators significantly affect genes involved in cancer initiation and maintenance. Recently, several clinical strategies targeting these epigenetic enzymes have emerged and some trials have demonstrated promising results for cancer treatment. Histone lysine demethylases (KDMs) yield distinct transcriptional outcomes that depend on the position of the methylated lysine and the specific genotype or lineage of the cancer cells. Due to their diverse roles in transcription, KDMs offer valuable opportunities for precision oncology, allowing treatments to be tailored to meet individual patient needs. This review emphasizes our current understanding of the functional relationship between KDMs and cancer as well as the development and application of small-molecule compounds that target KDMs.
Insights
Histone lysine demethylases (KDMs) are key epigenetic regulators in cancer. Targeting KDMs with small molecules offers promising precision oncology strategies for tailored cancer treatments.
Area of Science:
- Epigenetics and Molecular Biology
- Cancer Biology
- Pharmacology
Background:
- Epigenetic regulators (writers, erasers, readers) control gene expression via histone modifications.
- These regulators play critical roles in cancer initiation and progression.
- Emerging clinical strategies targeting epigenetic enzymes show promise in cancer therapy.
Purpose of the Study:
- To review the functional relationship between Histone Lysine Demethylases (KDMs) and cancer.
- To discuss the development and application of small-molecule compounds targeting KDMs.
- To highlight the potential of KDMs in precision oncology.
Main Methods:
- Literature review focusing on KDMs in cancer.
- Analysis of studies on small-molecule KDM inhibitors.
- Synthesis of current understanding of KDM functions in various cancer types.
Main Results:
- KDMs exhibit diverse roles in gene transcription, influencing cancer development.
- KDM activity and outcomes are dependent on methylated lysine position and cancer cell context.
- Small-molecule KDM inhibitors are being developed for therapeutic applications.
Conclusions:
- KDMs represent valuable targets for precision oncology due to their context-specific roles.
- Targeting KDMs offers opportunities for developing novel, tailored cancer treatments.
- Further research into KDM inhibitors could lead to significant advancements in cancer therapy.
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