Dr. Weeks’ Comment: Once again we learn that targeting caner STEM cells is better than chemo therapy (‘overcomes chemoresistance”) and inhibits metastases – so why are you still taking chemotherapy?
Targeting BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma
Bmi1+ CSCs mediate SCC initiation, invasive growth, and lymph node metastasis
Bmi+1 CSCs display increased AP-1 that drives SCC invasion and metastasis
Combinatorial targeting of Bmi1+ CSCs and tumor bulk overcomes chemoresistance in SCC
Eliminating Bmi1+ CSCs in SCC prevents metastasis
Squamous cell carcinoma in the head and neck (HNSCC) is a common yet poorly understood cancer, with adverse clinical outcomes due to treatment resistance, recurrence, and metastasis. Putative cancer stem cells (CSCs) have been identified in HNSCC, and BMI1 expression has been linked to these phenotypes, but optimal treatment strategies to overcome chemotherapeutic resistance and eliminate metastases have not yet been identified. Here we show through lineage tracing and genetic ablation that BMI1+ CSCs mediate invasive growth and cervical lymph node metastasis in a mouse model of HNSCC. This model and primary human HNSCC samples contain highly tumorigenic, invasive, and cisplatin-resistant BMI1+ CSCs, which exhibit increased AP-1 activity that drives invasive growth and metastasis of HNSCC. Inhibiting AP-1 or BMI1 sensitized tumors to cisplatin-based chemotherapy, and it eliminated lymph node metastases by targeting CSCs and the tumor bulk, suggesting potential regimens to overcome resistance to treatments and eradicate HNSCC metastasis.