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Research may lead to a more sophisticated approach to head and neck cancer




By targeting enzymes that play important roles in head and neck cancer cells, UCLA dentistry researchers have significantly slowed the growth and spread of tumors in mice, and the immunotherapy often received by these types of cancers. I was able to increase the effectiveness. It is resistant.

Their findings published online in the journal Molecular cellMay help researchers develop more sophisticated approaches to combat highly invasive head and neck squamous epithelial cancers that primarily affect the mouth, nose, and throat.

Immunotherapy, which is used as a clinical treatment for various cancers, utilizes the body’s natural defenses to fight the disease. However, some cancers, including head and neck squamous epithelial cancer, are less responsive to treatment than other cancers. The prognosis for these head and neck cancers is poor, the 5-year survival rate is high, and effective treatment is urgently needed.

The UCLA research team, led by Dr. Cun-Yu Wang, a prominent professor of oral biology at the University of Dental School, said tumors to immunotherapy by targeting tumor replication and the vulnerability of immune cell processes It has been shown that it may affect the reaction of cells.

The enzyme they focused on, KDM4A, is known as an epigenetic factor. It is a molecule that regulates gene expression, silences some genes in cells, and activates other genes. In head and neck cancer of squamous epithelial cells, overexpression of KDM4A promotes gene expression associated with cancer cell replication and diffusion.

It is well known that tumor cells can spread undetected by the immune system and can spread to lymph nodes or other parts of the body without supervision. In this case, tumor cells that develop in the epithelial layer that lines the structure of the head and neck can turn into head and neck squamous epithelial cancer if unchecked.

Cancer cell replication occurs through abnormal spread and activation of cancer cell signaling pathways, and researchers asked: If we can disrupt these processes and identify vulnerabilities, the body will fight against cancer cells. Is it possible to change the reaction of the body and the reaction to the outside? Immunotherapy?

We know that the KDM4A gene plays an important role in the replication and spread of cancer cells, so we focus on removing this gene and see if the opposite response is obtained. I did... “

Dr. Cun-Yu Wang, Research Author and Member of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles

By removing the KDM4A gene in their mouse model, researchers have witnessed a marked reduction in squamous cell carcinoma and much less cancer metastasis to the lymph nodes-a precursor to the spread of the disease throughout the body. ..

Surprisingly, they also found that removal of KDM4A also led to mobilization and activation of the fight against body infections. T cells, Killed cancer cells and stimulated endemic tumor immunity.

They then sought to clarify why squamous cell carcinoma cells were so unresponsive to immunotherapy treatment. In another series of mouse models, they again removed KDM4A and introduced PD-1 blockade. It signals the immunotherapeutic drug to attack the cancer cells. The combination of immunotherapy and KDM4A removal further reduced the growth of squamous cell carcinoma and lymph node metastasis.

Next, researchers tested whether small molecule inhibitors of KDM4A could be improved. Effectiveness of Original PD-1 blockade-based immunotherapy. They also found that inhibitors also helped to eliminate cancer stem cells associated with cancer recurrence.

This discovery holds promise for the development of more specific inhibitors and more effective cancer immunotherapies for KDM4A.

Dr. Paul Krebsbach, Dean and Professor of UCLA School of Dentistry, said: “The results of this study will have a significant impact on the development of more effective and life-saving cancer therapies.”


Journal reference:

Zhang, W. , et al.. (2021) Targeting KDM4A epigenetically activates tumor cell-specific immunity by inducing DNA replication stress...Molecular cell..


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