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Updated: Jun 29, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy
Subhanwita Sarkar1,2, Ayan Chanda2, Rutvij A Khanolkar1,2
1Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Abstract:
Polo-like-kinase-1 (PLK-1) is a serine/threonine kinase that regulates the cell cycle and acts as an oncogene in multiple cancers, including oral squamous cell carcinoma (OSCC). The loss of PLK-1 can inhibit growth and induce apoptosis, making it an attractive therapeutic target in OSCC. We evaluated the efficacy of PLK-1 inhibitors as novel, targeted therapeutics in OSCC. PLK-1 inhibition using BI6727 (volasertib) was found to affect cell death at low nanomolar concentrations in most tested OSCC cell lines, but not in normal oral keratinocytes. In cell lines resistant to volasertib alone, pre-treatment with radiotherapy followed by volasertib reduced cell viability and induced apoptosis. The combinatorial efficacy of volasertib and radiotherapy was replicated in xenograft mouse models. These findings highlight the potential of adding PLK-1 inhibitors to adjuvant therapy regimens in OSCC.
Insights
Targeting Polo-like-kinase-1 (PLK-1) with volasertib shows promise for oral cancer therapy. Combining volasertib with radiotherapy enhances efficacy in oral squamous cell carcinoma (OSCC) models.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Polo-like-kinase-1 (PLK-1) is a key cell cycle regulator and oncogene in various cancers, including oral squamous cell carcinoma (OSCC).
- PLK-1 inhibition offers a potential therapeutic strategy for OSCC due to its role in cancer cell growth and survival.
Purpose of the Study:
- To evaluate the efficacy of PLK-1 inhibitors as targeted therapeutics for OSCC.
- To investigate the combined effect of PLK-1 inhibition and radiotherapy in OSCC treatment.
Main Methods:
- In vitro assessment of PLK-1 inhibitor volasertib (BI6727) on OSCC cell lines and normal oral keratinocytes.
- Evaluation of volasertib combined with radiotherapy in resistant OSCC cell lines.
- In vivo validation using xenograft mouse models.
Main Results:
- Volasertib induced cell death in OSCC cell lines at low nanomolar concentrations, sparing normal cells.
- Radiotherapy pre-treatment followed by volasertib overcame resistance and enhanced apoptosis in OSCC cells.
- Combination therapy demonstrated efficacy in preclinical OSCC xenograft models.
Conclusions:
- PLK-1 inhibition with volasertib is a promising targeted therapy for OSCC.
- Combining volasertib with radiotherapy may represent a novel adjuvant therapeutic approach for OSCC.
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