DNA strand with stomach silhouette representing gastric cancer research

Gastric Cancer and DNA: Unlocking Targeted Therapies

Nico Varela in Health & Wellness July 2025 • 4 min read.

"A new review explores how DNA methylation impacts gastric cancer and opens doors to innovative treatment strategies."

Gastric cancer is a formidable health issue worldwide, ranking among the most frequent causes of cancer-related deaths. While genetic factors undoubtedly play a role, a growing body of research highlights the significance of epigenetic alterations, particularly DNA methylation, in the development and progression of this disease.

DNA methylation, a process catalyzed by DNA methyltransferases (DNMTs), is a well-characterized epigenetic hallmark in gastric cancer. Unlike genetic mutations that alter the DNA sequence, epigenetic modifications influence gene expression without changing the underlying code. Understanding these reversible alterations is crucial for developing effective therapeutic strategies.

A recent review delves into the intricate relationship between DNA methylation and gastric cancer. It explores key mechanisms, including the roles of SNPs, infections, and genetic modifications in triggering DNMTs level modification, and their subsequent impact on cancer progression. Crucially, the review focuses on how inhibitors of DNMTs can be strategically employed to combat gastric cancer, especially in cases of multidrug resistance.

How Does DNA Methylation Go Wrong in Gastric Cancer?

DNA strand with stomach silhouette representing gastric cancer research

Gastric cancer development involves both genetic and epigenetic changes, affecting oncogenes and tumor-suppressor genes (TSGs). While epigenetic modifications are normal during development and tissue differentiation, aberrant epigenetic modifications can disrupt cell function and contribute to cancer. These changes can alter the transcription levels of TSGs and oncogenes without altering DNA sequences.

Epigenetic alterations, including histone modification, noncoding RNA, and DNA methylation, can initiate and sustain changes that inactivate tumor-suppressor genes and other cancer-related genes in gastric cancer. Histone proteins, which determine chromatin structure and function, are modified through acetylation and methylation, affecting gene transcription, DNA replication, and nucleosome positioning.

Histone Hyperacetylation: Linked with transcriptional activation.
Histone Methylation: The effect depends on the specific amino acid residue modified and the degree of methylation; for example, trimethylation of H3K4 promotes gene expression, while trimethylation of H3K9 and H3K27 suppresses gene expression.
miRNAs: Small non-coding RNA molecules, are also key players in epigenetic regulation in gastric cancers. Dysregulation is associated with histone modifications and methylation patterns.

DNA methylation, a fundamental epigenetic mechanism, plays a crucial role in maintaining genomic stability through genomic imprinting and X-chromosome inactivation. Aberrant DNA methylation is strongly implicated in the development of various malignancies, including gastric cancer. Factors like age, diet, physical activity, chronic inflammation, and infectious agents can influence DNA methylation patterns in gastric epithelia. Global DNA hypo/hypermethylation commonly occurs in gastric tumors, contributing to genomic instability. Aberrant hyperactivation of DNA methyltransferases (DNMTs) is responsible for silencing or inactivating TSGs, driving cancer development.

The Future of Gastric Cancer Treatment: Targeting DNMTs

Gastric cancer remains a major cause of global morbidity and mortality, with epigenetic disruption playing a crucial role. Emerging evidence highlights the potential of targeting DNMTs to restore normal gene expression and overcome chemoresistance. While general and specific DNMT inhibitors show promise, the development of site-specific silencing strategies using CRISPR-Cas9 technology may offer even more precise and effective therapies for gastric cancer patients.

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Everything You Need To Know

What is DNA methylation, and why is it important in the context of gastric cancer?

DNA methylation is an epigenetic modification where a methyl group is added to a DNA molecule. This process, catalyzed by DNA methyltransferases (DNMTs), doesn't change the DNA sequence itself but can alter gene expression. In the context of gastric cancer, aberrant DNA methylation can lead to the silencing of tumor-suppressor genes (TSGs) or the activation of oncogenes, both of which contribute to cancer development and progression. It is significant because, unlike genetic mutations, DNA methylation is potentially reversible, making it a target for therapeutic intervention. Disruptions in DNA methylation patterns can have profound implications for genomic stability and cellular function, ultimately influencing the development and progression of gastric cancer.

What are DNMTs, and why is it important to understand their role in gastric cancer?

DNMTs, or DNA methyltransferases, are enzymes that catalyze the transfer of methyl groups to DNA, specifically to cytosine bases. They are crucial because they mediate DNA methylation, which plays a significant role in gene expression regulation. In gastric cancer, DNMTs are often hyperactivated, leading to abnormal DNA methylation patterns that silence tumor-suppressor genes (TSGs). Targeting DNMTs with inhibitors is a potential therapeutic strategy to restore normal gene expression and combat cancer. The implications of DNMT activity are substantial, as their dysregulation can drive cancer development and influence treatment response.

What are epigenetic modifications, and how do they affect gastric cancer?

Epigenetic modifications are changes in gene expression that do not involve alterations to the DNA sequence itself. These modifications, including DNA methylation, histone modification, and noncoding RNAs, are important because they can influence which genes are turned on or off. In gastric cancer, aberrant epigenetic modifications can lead to the silencing of tumor-suppressor genes (TSGs) or the activation of oncogenes, promoting cancer development and progression. These changes are potentially reversible, making them attractive targets for therapeutic intervention. The implications of epigenetic modifications are far-reaching, as they can alter cellular function and contribute to disease development.

Why is targeting DNMTs considered a promising approach for treating gastric cancer?

Targeting DNMTs holds promise as a therapeutic strategy for gastric cancer because DNMTs play a crucial role in aberrant DNA methylation, which can silence tumor-suppressor genes (TSGs) and promote cancer development. By inhibiting DNMTs, researchers aim to restore normal gene expression and reverse the epigenetic changes that drive cancer progression. This approach is particularly important in cases of multidrug resistance, where traditional therapies may not be effective. The development of site-specific silencing strategies using technologies like CRISPR-Cas9 may offer even more precise and effective therapies for gastric cancer patients.

What are histone modifications and what is their role?

Histone modifications are chemical alterations to histone proteins, which package and organize DNA within the nucleus. These modifications, such as acetylation and methylation, can influence chromatin structure and gene expression. Histone modifications are significant because they play a crucial role in regulating gene transcription, DNA replication, and nucleosome positioning. In gastric cancer, aberrant histone modifications can contribute to the silencing of tumor-suppressor genes (TSGs) or the activation of oncogenes, promoting cancer development and progression. These modifications can lead to changes that inactivate tumor-suppressor genes and other cancer-related genes, and also affect miRNAs, contributing to the disease. Understanding and targeting these modifications may offer new therapeutic avenues for gastric cancer.