Related Experiment Video
Updated: Nov 2, 2025
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Targeting cancer epigenetic pathways with small-molecule compounds: Therapeutic efficacy and combination therapies
Yi Wang1, Qiang Xie2, Huidan Tan3
1Health Management Center, Sichuan Provincial People' Hospital, University of Electronic Science and Technology of China, Chengdu 610072, PR China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, PR China.
Abstract:
Epigenetics mainly refers to covalent modifications to DNA or histones without affecting genomes, which ultimately lead to phenotypic changes in cells or organisms. Given the abundance of regulatory targets in epigenetic pathways and their pivotal roles in tumorigenesis and drug resistance, the development of epigenetic drugs holds a great promise for the current cancer therapy. However, lack of potent, selective, and clinically tractable small-molecule compounds makes the strategy to target cancer epigenetic pathways still challenging. Therefore, this review focuses on epigenetic pathways, small molecule inhibitors targeting DNA methyltransferase (DNMT) and small molecule inhibitors targeting histone modification (the main regulatory targets are histone acetyltransferases (HAT), histone deacetylases (HDACs) and histone methyltransferases (HMTS)), as well as the combination strategies of the existing epigenetic therapeutic drugs and more new therapies to improve the efficacy, which will shed light on a new clue on discovery of more small-molecule drugs targeting cancer epigenetic pathways as promising strategies in the future.
Insights
Epigenetic drugs offer promising cancer therapy by targeting DNA and histone modifications. This review explores small molecule inhibitors, combination strategies, and future drug discovery for epigenetic cancer pathways.
Area of Science:
- Molecular Biology
- Genetics
- Pharmacology
Background:
- Epigenetics involves modifications to DNA or histones, influencing phenotypes and playing key roles in cancer development and drug resistance.
- Targeting epigenetic pathways presents a promising avenue for cancer therapy due to numerous regulatory targets.
- Challenges remain in developing potent, selective, and clinically viable small-molecule epigenetic drugs.
Purpose of the Study:
- To review epigenetic pathways and their role in cancer.
- To discuss small molecule inhibitors targeting DNA methyltransferase (DNMT) and histone modifications (HATs, HDACs, HMTs).
- To explore combination strategies for epigenetic drugs and novel therapies to enhance efficacy.
Main Methods:
- Literature review of epigenetic pathways.
- Analysis of small molecule inhibitors targeting DNMTs.
- Review of inhibitors targeting histone acetyltransferases (HATs), histone deacetylases (HDACs), and histone methyltransferases (HMTs).
- Examination of combination therapeutic strategies.
Main Results:
- Epigenetic pathways are crucial in tumorigenesis and drug resistance.
- Small molecule inhibitors targeting DNMTs and histone modifications are under development.
- Combination therapies show potential for improved efficacy.
Conclusions:
- Developing effective small-molecule epigenetic drugs remains a challenge.
- Further research into epigenetic pathways and drug combinations is crucial for advancing cancer therapy.
- This review provides insights for future discovery of small-molecule drugs targeting cancer epigenetic pathways.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:38Mitogens and the Cell Cycle
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:26Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
02:18Cancer