How Epigenetic Therapies Differ From Chemotherapy in Lymphoma

Epigenetic therapies are offering a more targeted way to treat some lymphomas by changing how genes are turned on or off rather than broadly killing rapidly dividing cells like traditional chemotherapy.

In an interview with CURE, Dr. Jennifer Effie Amengual, a lymphoma specialist at Columbia University, explained that epigenetics refers to changes in how genes are expressed without altering the underlying DNA. Researchers can target enzymes that place small chemical marks along DNA and influence how it is packaged. These marks help control when DNA is “open” and able to be read to produce proteins.

Traditional chemotherapy works differently. It targets rapidly dividing cells and exploits vulnerabilities those cells need to survive. Because it is not highly selective, chemotherapy can also affect healthy cells that divide quickly, which can lead to side effects such as hair loss, nausea, decreased blood counts and infections.

Epigenetic drugs can still cause side effects, but they aim to take a more targeted approach by modifying abnormal gene expression patterns that drive certain lymphomas.

Amengual noted that these therapies do not work for every lymphoma subtype. Some lymphomas have disruptions in epigenetic regulation and may be particularly sensitive to epigenetic treatments, including follicular lymphoma, certain forms of diffuse large B-cell lymphoma and many T-cell lymphomas.

Transcript

Research focuses on developing combination epigenetic therapies for B-cell and T-cell lymphomas. For patients with lymphoma in 2026, what should they understand about how these newer targeted combinations differ from traditional chemotherapy?

Epigenetics refers to how we can change how genes are expressed without changing the genes themselves. “Epi” means “on top of,” and genes refer to DNA, or the blueprint for how proteins are produced. Epigenetics, therefore, describes changes that affect how genes are turned on or off without altering the underlying DNA.

We can influence epigenetics by targeting enzymes that place small chemical marks along DNA and the way DNA is packaged. These marks help control how DNA is read. One way to think about it is like a scroll: when the scroll is open, the DNA can be read and proteins can be produced. Epigenetic marks help control when and where that scroll opens and closes.

Because of this, epigenetic therapies can have broad effects on how genes are expressed.

Traditional chemotherapy works differently. It does not change how DNA is read. Instead, it targets rapidly dividing cells by exploiting weaknesses that these cells need to survive, ultimately killing them. Because chemotherapy is not highly targeted, it can also affect healthy cells that divide quickly. This is why many patients experience side effects such as hair loss, nausea, decreased blood counts and infections.

Epigenetic drugs are not free of side effects, but they tend to take a more targeted approach. However, they do not work for every type of lymphoma. Their effectiveness is often context dependent. Some lymphomas have disruptions in epigenetic regulation, and those types may be particularly sensitive to epigenetic therapies.

Examples include follicular lymphoma, some forms of diffuse large B-cell lymphoma and many T-cell lymphomas.

As a result, epigenetic therapies have been incorporated into the treatment of several lymphoma subtypes and have helped improve outcomes. These treatments work by correcting or modifying the abnormal patterns of gene expression that drive certain lymphomas.

Transcript has been edited for clarity and conciseness.

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