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Targeting cancer stem cells improves treatment effectiveness and prevents metastasis, UCLA study finds

Press releases may be edited for formatting or style | March 10, 2017 Rad Oncology
Targeting cancer stem cells may be a more effective way to overcome cancer resistance and prevent the spread of squamous cell carcinoma — the most common head and neck cancer and the second-most common skin cancer, according to a new study by cancer researchers at the UCLA School of Dentistry.

Head and neck squamous cell carcinoma is a highly invasive form of cancer and frequently spreads to the cervical lymph nodes. Currently, cisplatin is the standard therapeutic drug used for people with HNSCC. Yet, more than 50 percent of people who take cisplatin demonstrate resistance to the drug, and they experience a recurrence of the cancer. The five-year survival rates remain sorely low and researchers still don’t understand the underlying mechanisms behind head and neck squamous carcinoma. Therefore, said UCLA cancer biologist Dr. Cun-Yu Wang, who led the study, there’s an urgent need to understand why people with this type of cancer are resistant to therapy and to develop new approaches for treating it.

Wang’s research is published online today in the peer-reviewed journal Cell Stem Cell.
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Cancer stem cells are known to be responsible for tumor formation and development; they also self-renew and tend to be unresponsive to cancer therapy. These cells have been found in head and neck squamous cell carcinoma. Given the unique challenges that cancer stem cells pose for oncologists, it remains unclear what the optimal therapeutic strategy is for treating HNSCC.

To address this, Wang, who holds the Dr. No-Hee Park Endowed Chair in Dentistry at UCLA and holds a joint appointment in the UCLA Department of Bioengineering, and his research team first developed a mouse model of head and neck squamous cell carcinoma that allowed them to identity the rare cancer stem cells present in HNSCC using in vivo lineage tracing, a method to identify all progeny of a single cell in tissues.

The researchers found that the cancer stem cells expressed the stem cell protein Bmi1 and had increased activator protein-1, known as AP-1, a transcription factor that controls the expression of multiple cancer-associated genes. Based on these new findings, the UCLA team developed and compared different therapeutic strategies for treating head and neck squamous cell carcinoma. They found that a combination of targeting cancer stem cells and killing the tumor mass, consisting of high proliferating cells, with chemotherapy drugs resulted in better outcomes.

The team further discovered that cancer stem cells were not only responsible for squamous cell carcinoma development, but that they also cause cervical lymph node metastasis.

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