Halting Triple Negative Breast Cancer Spread: Restoring Order to Dividing Cancer Cells Reveals Potential Therapeutic Strategy

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October 4, 2025

Restoring Cell Order: A New Strategy to Halt Aggressive Breast Cancer Spread

Left: Normal cell division with chromosomes aligned. Right: faulty cell division with multiple centrosomes and chromosomal instability. Credit: Dr. Shelly Yang Bai

A groundbreaking study conducted by researchers at Weill Cornell Medicine presents a novel approach to combatting Triple Negative Breast Cancer (TNBC), one of the most challenging forms of the disease to treat. The examination reveals that an enzyme called EZH2 plays a critical role in driving abnormal cell division, a process that facilitates the spread of cancer to distant organs.

The preclinical research indicates that medications designed to block EZH2 could perhaps restore normalcy to cell division and effectively hinder the metastasis of TNBC cells. This finding offers a beacon of hope for patients facing this aggressive cancer.

The metastasis Challenge in Triple-Negative Breast cancer

According to leading experts, metastasis – the spread of cancer cells to other parts of the body – is the primary reason for poor survival rates among individuals diagnosed with TNBC. Dr. vivek Mittal, a prominent researcher involved in the study, emphasized that their work suggests a new therapeutic strategy focused on preventing metastasis before it begins, potentially improving outcomes for patients.

the research challenges conventional thinking in cancer treatment which previously focused on exacerbating existing cell division errors to induce cell death. The study, published in cancer finding, demonstrates that controlling, rather than amplifying, chromosomal instability is a more effective approach.

Normal cell division relies on the precise duplication and separation of chromosomes. Though, in many cancer cells, this process becomes chaotic, leading to chromosomal instability – an imbalance in the number or structure of chromosomes.Dr. Mittal cautions that simply increasing this instability could paradoxically worsen the disease, suggesting the need for a more nuanced strategy.

Unveiling the Role of EZH2

Approximately 5% of cells within a primary TNBC tumor possess a high propensity to metastasize. These cells exhibit distinct characteristics, including altered metabolism, heightened chromosomal instability, and modified epigenetics – changes affecting gene expression without altering the underlying DNA code.

The research team identified EZH2 as a key culprit driving metastasis in these cells.Under normal circumstances, EZH2 regulates DNA packaging. However, cancer cells often hijack this process, increasing EZH2 production, which then silences essential genes required for proper chromosome segregation during cell division, leading to widespread errors.

Analysis of data from breast cancer patients revealed a correlation: higher levels of EZH2 were associated with increased chromosomal alterations in tumor cells. Further laboratory experiments confirmed that inhibiting EZH2 with the FDA-approved drug tazemetostat reduced chromosomal instability, while boosting EZH2 levels genetically increased errors in cell division. Mouse models corroborated these findings,showing that tumors with elevated EZH2 levels exhibited increased lung metastasis.

Factor	Effect on Metastasis
High EZH2 Levels	Increased chromosomal instability & metastasis
Inhibiting EZH2	Reduced chromosomal instability
Boosting EZH2 Levels	Increased errors in cell division

The Mechanism of Chromosomal Chaos

The researchers pinpointed a specific mechanism by which EZH2 drives instability: it silences the tankyrase 1 gene. this gene typically ensures the proper functioning of the chromosome-separating machinery during cell division. When tankyrase 1 is suppressed, another protein, CPAP, accumulates excessively, causing the centrosomes – structures responsible for pulling chromosomes apart – to multiply uncontrollably. This results in faulty cell divisions, creating cells with an incorrect number of chromosomes.

By inhibiting EZH2, the team was able to restore balance, significantly reducing metastasis in preclinical models. “For the first time, we have linked EZH2, which is an epigenetic regulator, with chromosomal instability in a mechanistic fashion,” explained Dr. Shelley Yang Bai, the study’s first author.

This research suggests that EZH2 inhibitors may be the first drugs capable of directly suppressing chromosomal instability. dr. Magdalena Plasilova, a surgical oncologist involved in the study, expressed optimism that this discovery offers a promising new approach to treating TNBC by addressing the root cause of metastasis.

While tazemetostat shows promise,researchers believe that other drugs may prove even more effective. Dr. Mittal indicated that this discovery paves the way for clinical trials to test EZH2 inhibitors, not only in high-risk breast cancer but also in other cancers characterized by chromosomal instability, such as lung adenocarcinoma.

Understanding Epigenetics and Cancer

Epigenetics, the study of changes in gene expression without alterations to the DNA sequence itself, is increasingly recognized as a pivotal factor in cancer progress and progression. Unlike genetic mutations, epigenetic modifications are often reversible, presenting new avenues for therapeutic intervention. Recent data from the National Cancer Institute suggests epigenetic alterations are found in over 80% of cancers, highlighting their importance in disease development.

Did You Know? Targeting epigenetic changes, such as those mediated by EZH2, is a rapidly growing field of cancer research, with numerous clinical trials underway exploring the potential of epigenetic drugs.

Pro Tip: Staying informed about the latest advancements in cancer research, including epigenetic therapies, can empower you to have informed discussions with your healthcare provider.

Frequently Asked Questions about EZH2 and Breast cancer

• What is EZH2 and how does it relate to cancer? EZH2 is an enzyme that regulates DNA packaging. In cancer, its overproduction can lead to chromosomal instability and increased metastasis.
• What is chromosomal instability? chromosomal instability refers to an abnormal number or structure of chromosomes in cells, often seen in cancer.
• What is triple-negative breast cancer (TNBC)? TNBC is an aggressive form of breast cancer that lacks expression of estrogen receptors, progesterone receptors, and HER2 protein, making it tough to treat with traditional therapies.
• How could EZH2 inhibitors help treat TNBC? EZH2 inhibitors aim to restore order to cell division by blocking the enzyme’s activity, potentially preventing metastasis.
• What are the next steps in this research? The next steps involve conducting clinical trials to assess the safety and efficacy of EZH2 inhibitors in patients with high-risk breast cancer and other cancers with chromosomal instability.
• Is tazemetostat currently approved to treat TNBC? While tazemetostat is FDA-approved for certain cancers, it is not yet approved specifically for the treatment of TNBC.
• What does metastasis mean? Metastasis is the spread of cancer cells from the primary tumor to other parts of the body.

What are your thoughts on this potential breakthrough in treating triple-negative breast cancer? Do you believe targeting epigenetic factors like EZH2 will become a standard approach in cancer therapy?

Share your comments below and help us spread awareness of this critically important research!