Targeting cancer stem cells may be a more effective way to overcome cancer resistance and prevent the spread of squamous cell carcinoma, which is the most common head and neck cancer and the second most common skin cancer, according to the University of California Los Angeles (UCLA) School of Dentistry.
Cisplatin is the standard therapeutic drug for people with head and neck squamous cell carcinoma (HNSCC). Yet more than 50% of people who take it demonstrate resistance to it, UCLA reports, and experience a recurrence of the cancer. Also, 5-year survival rates remain low, and researchers still don’t understand the underlying mechanisms behind the cancer.
Cun-Yu Wang, DDS, PhD, a cancer biologist at UCLA who led the study, says that’s why there’s an urgent need to understand why people with this type of cancer are resistant to therapy and to develop new approaches to treating it. He and his team began with a mouse model of HNSCC that enabled them to identify the rare cancer stem cells present in it using in vivo lineage tracing, a method that identifies all progeny of a single cell in tissues.
The cancer stem cells expressed the stem cell protein Bmi1 and had increased activator protein-1 (AP-1), a transcription factor that controls the expression of multiple cancer-associated genes. Based on these findings, the researchers developed and compared different therapeutic strategies for treating HNSCC.
The researchers 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. They also discovered that cancer stem cells not only were responsible for SCC development, but that they also cause cervical lymph node metastasis.
“This study shows that for the first time, targeting the proliferating tumor mass and dormant cancer stem cells with combination therapy effectively inhibited tumor growth and prevented metastasis compared to monotherapy in mice,” said Wang. “Our discovery could be applied to other solid tumors such as breast and colon cancer, which also frequently metastasizes to lymph nodes or distant organs.”
“The work has important translational values,” said Paul Krebsbach, DDS, PhD, dean of the UCLA School of Dentistry. “Small molecule inhibitors for cancer stem cells in this study are available or being utilized in clinical trials for other diseases. It will be interesting to conduct a clinical trial to test these inhibitors for HNSCC.”
The study, “Targeting BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma,” was published by Cell Stem Cell and supported in part by grants from the National Institute of Dental and Craniofacial Research.
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