Targeting epigenetics for cancer therapy

Abstract

Cancer can be identified as a chaotic cell state, which breaks the rules that govern growth and reproduction, with main characteristics such as uncontrolled division, invading other tissues, usurping resources, and eventually killing its host. It was once believed that cancer is caused by a progressive series of genetic aberrations, and certain mutations of genes, including oncogenes and tumor suppressor genes, have been identified as the cause of cancer. However, piling evidence suggests that epigenetic modifications working in concert with genetic mechanisms to regulate transcriptional activity are dysregulated in many diseases, including cancer. Cancer epigenetics explain a wide range of heritable changes in gene expression, which do not come from any alteration in DNA sequences. Aberrant DNA methylation, histone modifications, and expression of long non-coding RNAs (lncRNAs) are key epigenetic mechanisms associated with tumor initiation, cancer progression, and metastasis. Within the past decade, cancer epigenetics have enabled us to develop novel biomarkers and therapeutic target for many types of cancers. In this review, we will summarize the major epigenetic changes involved in cancer biology along with clinical and preclinical results developed as novel cancer therapeutics.

Epigenetic Modification of CFTR in Head and Neck Cancer

“…Cancer epigenetics, the study of epigenetic modifications to genes affecting cellular phenotypes of cancer cells by mechanisms other than changes to DNA sequence, has been actively studied within the past two decades and uncovered novel biomarkers and therapeutic targets for most type of cancers [42][43][44][45]. Even the molecular alterations causing diverse malignancy traits can be deeply influenced by epigenetic changes [42].…”

“…Even the molecular alterations causing diverse malignancy traits can be deeply influenced by epigenetic changes [42]. Epigenetic modification including histone modification, non-coding RNA regulation, and aberrant DNA methylation have been associated with tumor initiation, cancer progression, and metastasis [44]. To date, methylation is the most well-studied mechanism in epigenetic modification.…”

Epigenetic Research in Stem Cell Bioengineering—Anti-Cancer Therapy, Regenerative and Reconstructive Medicine in Human Clinical Trials

“…Heritable changes in gene function, including epigenetic regulatory mechanisms such as DNA methylation and histone modification, play an important role in cancer progression [82]. Recently, epigenetic modifications were highlighted as a novel and significant hallmark for assaying various types of cancer.…”

Targeting Epigenetic Dependencies in Solid Tumors: Evolutionary Landscape Beyond Germ Layers Origin

“…This definition has evolved over time, and, nowadays, the concept has been extended to a wide range of cellular processes and cell states determined by hereditary chromatin structure and not directly determined by alterations of DNA sequence [2]. Thus, the study of chromatin architecture and spatial distribution, exactly as the DNA sequence, is posed in the center of evolution, profoundly altering gene expression patterns through the compactness and accessibility of DNA [3,4]. In this context, chromatin is the macromolecular complex of DNA and histone proteins, which provides the scaffold for the efficient packaging of 3 billion pair length of human DNA into a~10-µm cell nucleus [2,5].…”