Precision epigenetic therapies in oncology
Arundhati Chaudhary1, Kayleigh J A Orchard2, Francesca Salani2,3,4
1Cancer Research Group, School of Life, Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA, UK. arundhatichaudhary101099@gmail.com.
Abstract:
Phenotypic plasticity is a key mechanism of metastatic progression and cancer therapy resistance. This hallmark of human malignancies is enabled by highly conserved epigenetic mechanisms that control gene expression. Functional alterations in DNA methylation and histone post-translational modifications have been extensively described as drivers of metastatic dissemination and therapy resistance. Pharmacological inhibitors of epigenetic enzymes can revert these alterations, thereby stopping cancer progression and counteracting the emergence of resistant clones. Despite promising pre-clinical evidence, the clinical implementation of epigenetic therapies in solid cancers has led to disappointing results. Several factors can explain these challenges, including the lack of rational combinations. Notably, response to epigenetic treatments can be heterogeneous and short-lived. A liquid biopsy technology that allows the measure of specific epigenetic alterations enables patient selection and therapy monitoring, leading to the development of precision epigenetic therapies. In this review, we discuss the state of the art of this emerging treatment modality, and we identify key challenges that need to be overcome to reach the full potential of this new therapeutic concept.
Insights
Epigenetic mechanisms drive cancer metastasis and therapy resistance. Precision epigenetic therapies using liquid biopsies show promise but face challenges in clinical application.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Phenotypic plasticity, driven by epigenetic mechanisms like DNA methylation and histone modifications, is crucial for cancer metastasis and therapy resistance.
- Epigenetic alterations are key drivers of cancer progression and the development of drug-resistant clones.
- Pharmacological targeting of epigenetic enzymes offers a potential strategy to reverse these alterations.
Purpose of the Study:
- To review the current state of precision epigenetic therapies in solid cancers.
- To identify challenges hindering the clinical implementation of epigenetic treatments.
- To explore the role of liquid biopsy in patient selection and therapy monitoring for epigenetic therapies.
Main Methods:
- Review of current literature on epigenetic mechanisms in cancer.
- Analysis of pre-clinical and clinical data on epigenetic therapies.
- Discussion of liquid biopsy technologies for epigenetic alteration detection.
Main Results:
- Epigenetic therapies show promise pre-clinically but have yielded disappointing clinical results in solid tumors.
- Challenges include the need for rational drug combinations and overcoming heterogeneous, short-lived treatment responses.
- Liquid biopsy technology enables patient stratification and monitoring, paving the way for precision epigenetic therapies.
Conclusions:
- Precision epigenetic therapies, guided by liquid biopsy, represent an emerging modality for cancer treatment.
- Overcoming challenges in rational combinations and response heterogeneity is crucial for realizing the full potential of epigenetic therapies.
- Further research is needed to optimize the clinical application of these novel therapeutic strategies.
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