Evaluation of in vitro and in vivo personalized cancer treatment assays for oral squamous cell carcinoma

Wafa Wahbi; Katja Korelin; Meri Sieviläinen; Peeter Karihtala; Tommy Wilkman; Jussi Tarkkanen; Tuula Salo; Ahmed Al-Samadi

doi:10.1016/j.tranon.2023.101677

Evaluation of in vitro and in vivo personalized cancer treatment assays for oral squamous cell carcinoma

Transl Oncol. 2023 Jul:33:101677. doi: 10.1016/j.tranon.2023.101677. Epub 2023 Apr 25.

Authors

Wafa Wahbi¹, Katja Korelin¹, Meri Sieviläinen¹, Peeter Karihtala², Tommy Wilkman³, Jussi Tarkkanen⁴, Tuula Salo⁵, Ahmed Al-Samadi⁶

Affiliations

¹ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki 1, C223b, Haartmaninkatu 8, P.O. Box 63, Helsinki 00014, Finland; Translational Immunology Research Program (TRIMM), Faculty of Medicine, University of Helsinki, Biomedicum Helsinki 1, Haartmaninkatu 8, P.O. Box 63, Helsinki 00014, Finland.
² Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, P.O. Box 180, Helsinki 00029, Finland.
³ Department of Oral and Maxillofacial Surgery, HUS Helsinki University Hospital, P.O. Box 281, Helsinki 00029, Finland.
⁴ Department of Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, P.O. Box 21, Helsinki, 00014, Finland.
⁵ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki 1, C223b, Haartmaninkatu 8, P.O. Box 63, Helsinki 00014, Finland; Translational Immunology Research Program (TRIMM), Faculty of Medicine, University of Helsinki, Biomedicum Helsinki 1, Haartmaninkatu 8, P.O. Box 63, Helsinki 00014, Finland; Department of Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, P.O. Box 21, Helsinki, 00014, Finland; Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, P.O. Box 5281, Oulu 90014, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5281, Oulu 90014, Finland.
⁶ Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki 1, C223b, Haartmaninkatu 8, P.O. Box 63, Helsinki 00014, Finland; Translational Immunology Research Program (TRIMM), Faculty of Medicine, University of Helsinki, Biomedicum Helsinki 1, Haartmaninkatu 8, P.O. Box 63, Helsinki 00014, Finland. Electronic address: ahmed.al-samadi@helsinki.fi.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a common cancer with a high heterogeneity and few approved treatments. OSCC is one of the least explored areas for precision oncology. In this study, we aimed to test the reliability of our three established rapid cancer systemic treatment-testing assays: human tumour-derived matrix (Myogel)-coated well-plates, zebrafish xenografts, and 3D microfluidic chips.

Methods: Chemo-, radio- and targeted-therapy testing in Myogel-coated wells and zebrafish xenografts was conducted nine times using five samples; two primary and three metastatic lymph node samples from three OSCC patients. Peripheral blood mononuclear cells (PBMNCs) were isolated from the patients' blood. The response of the tumour cells to radio-, chemo-, and targeted therapy was tested using Myogel-coated wells and zebrafish larvae xenografts. The tumour cells' response to immunotherapy was tested using 3D microfluidic chips. The cells' sensitivity to the treatments was compared with the patients' clinical response. Primary and metastatic lymph node tissue-derived DNA samples from two patients underwent whole exome sequencing to compare the mutational profiles of the samples.

Results: Test results were in line with patients' responses in 7/9 (77%) zebrafish xenograft assays and 5/9 (55%) Myogel-coated wells assays. Immunotherapy testing was done using one metastatic patient sample which matched the patients' response. Differences in responses to treatments between primary and metastatic samples of the same patient were detected in 50% of the zebrafish larvae assays.

Conclusions: Our results show the potential of using personalized cancer treatment testing assays - specifically zebrafish xenografts that revealed promising results - in OSCC patient samples.

Keywords: Microfluidic chip; Myogel; Oral cancer; Personalized medicine; Zebrafish.