Insights on Bmi-1 therapeutic targeting in head and neck cancers

The B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) protein of the polycomb complex is an essential mediator of the epigenetic transcriptional silencing by the chromatin structure. It has been reported to be crucial for homeostasis of the stem cells and tumorigenesis. Though years of investigation have clarified Bmi-1's transcriptional regulation, post-translational modifications, and functions in controlling cellular bioenergetics, pathologies, and DNA damage response, the full potential of this protein with so many diverse roles are still unfulfilled. Bmi-1 is overexpressed in many human malignancies. Unraveling the Bmi-1's precise functional role in head and neck cancers can be attractive for mechanisms-based developmental therapeutics. This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on the role that Bmi-1 plays in oral cancer progression and evaluates how this can be used in advancing clinical treatment strategies for head and neck cancer. Bmi-1 is a promising target for therapy because it has been linked to a stemness and oncogenesis signature. However, to use Bmi-1 as a prognostic marker and a therapeutic target in the long run, new methods are imperative for further characterization of the physiological roles of Bmi-1. Current biological insights of Bmi-1 as a master regulator of stem cell self-renewal have emerged as a prominent player in cancer stem cell (CSC) biology. Bmi-1+ cells mediate chemoresistance and metastasis. On the other hand, inhibiting Bmi-1 rescinds CSC function and re-sensitizes cancer cells to chemotherapy. Therefore, elucidating therapeutic approaches targeting Bmi-1 can be leveraged to further research analysis to advance clinical treatment strategies for head and neck cancer.