The significance of epigenetics and precision medicine in the context of uncommon cancers, referred to as "rare cancers," is investigated in this chapter.A comprehensive review of the current literature on noncoding RNAs (ncRNAs), natural products, and clinical trials specific to uncommon cancers was conducted. The role of ncRNAs in tumor biology is elaborated, revealing their dual influence on tumor suppression and oncogenesis, alongside current therapeutic strategies targeting these molecules. Recent clinical trial outcomes were analyzed to assess therapeutic potentials and innovations. The role of epigenetic mechanisms in rare cancer development and treatment, particularly focusing on how natural products can modify epigenetic mechanisms, such as DNA methylation, histone modifications, and the regulation of ncRNAs, was discussed in detail. The chapter emphasizes the potential of these natural products as therapeutic agents, or "epi-drugs," in cancer prevention and treatment.
Epigenetic modifications function as central controllers of gene expression in cancer, coordinating crucial cellular activities that trigger the initiation and progression of the tumor, besides their importance in therapeutic response. These modifications can control the gene expression without changing the sequence of DNA. In colorectal cancer (CRC), these alterations involving DNA methylation, histone modifications, chromatin rearrangement, and noncoding ribonucleic acids play a significant role in the pathogenesis of CRC. Abnormal DNA methylation silences the tumor suppressor genes, meanwhile leading to the instability of the genome via reduction of the whole methylation. Specific methylation signatures, such as CpG islands, help in categorizing the subtypes of the tumor and predicting the clinical outcomes. In addition, histone-modifying enzymes, including enhancer of zeste homolog 2 and histone deacetylases, are frequently uncontrolled in cancer, leading to alterations in gene expression. Moreover, small regulatory ribonucleic acids such as microRNA-21 and microRNA-143 contribute to the complex networks that regulate cell survival and growth. Collectively, these epigenetic alterations trigger the transition from benign growth to malignant cancer by continuously suppressing crucial genes. Furthermore, the epigenetic markers can be detected in blood and stool specimens, offering promising tools for the early detection of cancer. The major obstacle in cancer treatment is the resistance to chemotherapy drugs, which is mainly caused by epigenetic modifications in cancer cells. Therefore, the new therapeutic ways target the modifications that occur in DNA methylation and histone, mostly in conjunction with conventional therapies. As the metabolites produced by the gut microbiome can alter the host epigenetics, they can promote cancer development. Promising technologies help in the concise proofreading of epigenetic marks, and advanced single-cell analysis is paving the way for personalized treatment approaches. This cutting-edge knowledge of epigenetic regulation mechanisms offers new prospects for enhancing diagnosis, prognosis, and targeted therapies in colorectal cancer.
There is an urgent need for reliable noninvasive indicators of the occurrence and course of liver disease. According to research conducted in recent decades, the risk scores for liver-related complications can be determined by utilizing the genetic and epigenetic components involved in the development of liver disease. This might potentially indicate the feasibility of implementing programs for target screening and monitoring of complications.Precision medicine may be used to treat liver illnesses, thanks to recent advancements in our knowledge of the epigenetics of liver cells. In a multicellular organism, each cell has a distinct phenotype, even if they all have the same genetics. Chromatin states determined by epigenetic processes are necessary for this heritable yet dynamic cell identity. Genetic, environmental, and metabolic factors that determine DNA accessibility to the transcriptional machinery governing gene expression and cellular states in various liver illnesses can alter the epigenomic landscapes unique to the liver. Noncoding RNAs (ncRNAs) are examples of the epigenetic regulation of chromatin. The coordinated actions of numerous epigenetic factors that modify nucleosome positioning and structure (remodelers), create epigenetic marks in DNA and histones (writers), identify and interpret the marks (readers), and eliminate these marks (erasers) preserve this epigenetic information.Here, we summarize the literature on how epigenetic changes contribute to the development of liver cancers. Along with talking about the potential of epigenetic therapy approaches, we also address their usefulness as epigenetic biomarkers for the diagnosis and prognosis of hepatocellular carcinoma.
Breast cancer remains a leading cause of cancer-related morbidity and mortality in women worldwide. While extensive research has focused on mutations in protein-coding genes, emerging evidence underscores the pivotal role of the noncoding genome-including long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs)-in tumorigenesis, progression, and therapeutic resistance. These noncoding RNAs (ncRNAs) are regulated through diverse epigenetic mechanisms such as DNA methylation, histone modifications, and N6-methyladenosine (m6A) RNA methylation. Aberrant epigenetic modifications in noncoding regions can silence tumor suppressors or activate oncogenes, thereby reprogramming cellular behavior and contributing to breast cancer heterogeneity. High-throughput techniques like whole-genome bisulfite sequencing (WGBS), ATAC-seq, and ChIP-seq have facilitated the discovery of noncoding epimutations with clinical significance. Moreover, ncRNA-based epigenetic alterations are increasingly explored as diagnostic biomarkers, prognostic indicators, and therapeutic targets, particularly in subtype-specific contexts such as triple-negative breast cancer (TNBC) and HER2-positive tumors. Despite advances, challenges remain in interpreting functional noncoding elements and translating findings into clinical interventions. This chapter provides a comprehensive examination of the noncoding epigenome in breast cancer, highlighting current methodologies, molecular mechanisms, and translational potential while also identifying future directions needed to leverage noncoding epigenetics for personalized cancer care.
