UCLA researchers in the Department of Dentistry discovered that targeting BMI1in head and neck squamous cell carcinoma (HNSCC) may be a viable immune checkpoint to inhibit metastatic tumor growth, and prevent tumor relapse through activation of cell-intrinsic immunity and purging cancer stem cells (CSCs).
BACKGROUND:
Cancer stem cells are cancer initiating cells, that are known to be associated with tumor initiation, growth and metastasis. Moloney murine leukemia virus insertion site (BMI1) is known to control the self-renewal potential and function of SCS in human cancers, such as HNSCC, which account for over 1 million new cancer cases worldwide each year and has a low 5-year survival rate. The HNSCC current standard of care, which includes the small molecule inhibitor, PTC209, has had some success in eliminating the self-renewal potential of CSCs. However, the median response duration rate is short and an alternative treatment for HNSCC is still needed.
INNOVATION:
Researchers at UCLA led by Dr. Cun-Yu Wang have established a powerful mouse model of HNSCC that fully mimics how HNSCC develops and metastasizes in humans. The Wang lab used this model to trace BMI1+ CSC with a combination of BMI1 inhibitors, and discovered that inhibition of BMI1 eliminated BMI1+ CSC and augmented PD1 blockade through activation of tumor cell-intrinsic immunity. This resulted in an inhibition of metastatic tumor growth and fully prevented a tumor relapse.
POTENTIAL APPLICATIONS:
- Treat and prevent recurrent and metastatic HNSCC
- Reduction in HNSCC relapse and lymph node metastasis
- BMI1 may be a new strategy of the combination therapy in order to effectively inhibit metastatic tumor growth and prevent relapse
ADVANTAGES:
- More effective HNSCC treatment than the standard anti-PD1 plus cisplatin treatment
- Induces tumor cell-intrinsic immune responses by activating CD8+ T cells
- Combination therapy of BMI1 inhibition and anti-PD1 effectively inhibits tumor growth metastasis by eliminating CSCs
DEVELOPMENT-TO-DATE:
UCLA researchers used mouse xenograft models
Related Papers (from the inventors only)
Jia, L., Zhang, W., Cun-Yu, W. BMI1 Inhibition Eliminates Residual Cancer Stem Cells after PD1 Blockade and Activates Antitumor Immunity to Prevent Metastasis and Relapse. Cell Stem Cell. 2020. 27(2):238-253.