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Epidrugs in cancer: mechanisms, applications, and future direction
Roshni Bibi1, Lakshmi Varshetha1, Rakshit Kamal Lahary1
1Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai, Tamil Nadu, 603203, India.
Abstract:
DNA methylation, histone modifications, and regulation of non-coding RNA are all epigenetic modifications affecting cancer cells of origin and progression. These changes lead to changed expression of genes, which in turn is the reason for cancer occurrence in the form of inhibition of tumor suppressor genes or activation of oncogenes. Epigenetic changes, as opposed to genetic mutations, are reversible; thus, they seem to be interesting targets for therapeutic interventions. Current review summarizes the various types of epidrugs -DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors (HMTis), and BET inhibitors-are studied in this review. And the mechanisms of action, therapeutic potential, and clinical applications of epidrugs in several types of cancer, such as solid tumors (breast, lung, colorectal, and brain tumors) and hematological malignancies (acute myeloid leukemia (AML) and multiple myeloma). In addition, we address the challenges faced by epigenetic therapies, such as drug toxicity, off-target effects, and drug resistance. One of the rapidly evolving areas of cancer treatment is bringing new cancer treatments, and the use of epidrugs with conventional treatments, immunotherapy, and targeted therapy is an area. Epidrugs, drugs that control epigenetic pathways, have become substances that could be beneficial in cancer treatment. They can repress normal gene expression, reverse drug resistance, and make tumors penetrable to treatments that are already in place. Following instructions by tumor-specific epigenome analysis, personalized epigenetic therapy has the prospect to tailor the treatment schedule and to enhance medical outcome. Overcoming limitations and forming combination strategies to promote efficacy with less toxicity would foster the epigenetic treatment approach for cancer.
Insights
Epigenetic modifications influence cancer development and are reversible, making them promising therapeutic targets. This review explores epidrugs like DNMTis and HDACis, their mechanisms, and clinical applications in various cancers.
Area of Science:
- Epigenetics and Cancer Biology
- Pharmacology and Therapeutics
Background:
- Epigenetic modifications (DNA methylation, histone modifications, non-coding RNA regulation) are crucial in cancer initiation and progression.
- These reversible changes offer therapeutic opportunities distinct from genetic mutations.
Purpose of the Study:
- To review various classes of epidrugs, including DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors (HMTis), and BET inhibitors.
- To summarize the mechanisms of action, therapeutic potential, and clinical applications of these epidrugs across diverse cancers.
- To address challenges and future directions for epigenetic therapies in oncology.
Main Methods:
- Comprehensive literature review of epidrugs targeting epigenetic pathways.
- Analysis of preclinical and clinical data on epidrug efficacy and toxicity.
- Exploration of combination strategies with conventional therapies, immunotherapy, and targeted treatments.
Main Results:
- Epidrugs demonstrate potential in treating solid tumors (breast, lung, colorectal, brain) and hematological malignancies (AML, multiple myeloma).
- These drugs can reverse gene silencing, overcome drug resistance, and enhance tumor sensitivity to existing treatments.
- Challenges include drug toxicity, off-target effects, and acquired resistance, necessitating careful management.
Conclusions:
- Epidrugs represent a significant advancement in cancer treatment, offering novel mechanisms to control aberrant gene expression.
- Personalized epigenetic therapy, guided by tumor-specific epigenome analysis, holds promise for tailored treatment strategies.
- Overcoming current limitations through combination therapies and addressing toxicity are key to maximizing the clinical benefit of epigenetic approaches in cancer care.
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