Interested in Overcoming Chemo-resistence?

Interested in Overcoming Chemo-resistence?

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?

 

Cell Stem Cell

Available online 9 March 2017

In Press, Corrected Proof — Note to users

Article

Targeting BMI1+ Cancer Stem Cells Overcomes Chemoresistance and Inhibits Metastases in Squamous Cell Carcinoma


Highlights

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


Summary

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.

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