Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy

Subhanwita Sarkar; Ayan Chanda; Rutvij A Khanolkar; Meghan Lambie; Laurie Ailles; Scott V Bratman; Aru Narendran; Pinaki Bose

doi:10.3390/biomedicines12030503

Targeting Oral Squamous Cell Carcinoma with Combined Polo-Like-Kinase-1 Inhibitors and γ-Radiation Therapy

Biomedicines. 2024 Feb 23;12(3):503. doi: 10.3390/biomedicines12030503.

Authors

Subhanwita Sarkar^{1

2}, Ayan Chanda², Rutvij A Khanolkar^{1

2}, Meghan Lambie^{3

4}, Laurie Ailles^{3

4}, Scott V Bratman^{3

4

5}, Aru Narendran^{1

2

6}, Pinaki Bose^{1

2

7}

Affiliations

¹ Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
² Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB T2N 4N1, Canada.
³ Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada.
⁴ Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
⁵ Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada.
⁶ Department of Pediatrics, University of Calgary, Calgary, AB T2N 4N1, Canada.
⁷ Ohlson Research Initiative, Arnie Charbonneau Cancer Institute, 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.

Keywords: OSCC; polo-like-kinase-1; volasertib; γ-radiation therapy.

Grants and funding

This work was supported by funds from the Calgary Foundation and the Ohlson Research Initiative, University of Calgary.