High-throughput In Vitro Drug Sensitivity Detection Based On The Construction Of Patient-derived Tumor Cell Model Of Oral Squamous Cell Carcinoma

ObjectiveSquamous cell carcinoma is also called the epidermis,happens at adnexal or epidermal cells,belongs to a kind of malignant tumor,usually occurs in the place such as oral cavity,esophagus,skin,including the relatively high incidence of oral squamous cell carcinoma to the current one and maxillofacial malignant tumor,the integrated sequence treatment such as surgery,radiotherapy and chemotherapy has become a consensus.The aim of this study was to construct a patient-derived tumor cell（PDC）model of oral squamous cell carcinoma using fresh tumor tissue from patients and apply it to the high-throughput drug sensitivity assay of oral squamous cell carcinoma patients.We evaluated the in vitro efficacy of 116 drugs,including chemotherapy monotherapies,targeted agents,immunomodulators,glucocorticoids,and traditional Chinese medicine,and graded the sensitivity of drugs to provide a reference for the precise drug use in oral squamous cell carcinoma patients.MethodsTo meet the exclusion criteria and the patient’s informed consent,20 samples of cancer and paracancerous tissues of oral squamous cell carcinoma patients hospitalized in the Oral and Maxillofacial Surgery Ward of the First Affiliated Hospital of Anhui Medical University were collected intraoperatively,and the removed tumor tissues were transported by cold chain to the PRECEDO pharmaceuticals Co.Ltd to establish a Patientderived tumor cell model and to screen chemotherapeutic drugs and targeted drugs based on high-throughput in vitro drug sensitivity assay technology.The inhibition rate was calculated to evaluate the in vitro killing effect of the drugs on the autologous cancer cells of the subject.The sensitivity of chemotherapeutic drugs was graded according to the magnitude of the inhibition rate.ResultsAmong the in vitro drug sensitivity assay results of 20 cases of oral squamous cell carcinoma primary cells,a total of 31 chemotherapeutic drugs exhibited highly sensitive（inhibition rate ≥ 80%）results.Among the results of the percentage frequency of sensitivity（inhibition rate ≥ 20%）to 116 chemotherapeutic drugs,a total of 18 drugs with a percentage frequency of sensitivity greater than or equal to 70% were: Romidepsin,Mitoxantrone,Venetoclax,Panobinostat,Idelalisib,Lenalidomide,Cytarabine,Ceritinib,Lenvatinib,Baicalein,Quercetin,Teniposide,Gefitinib,Cobimetinib,Astragaloside III,Oleanolic Acid,Belinostat,Bleomycin.The individual sensitivity rates of 20 patients to116 drugs were different.There are differences in the sensitive drug spectrum of patients.ConclusionDifferences in drug sensitivity exist among individual patients,and individualized therapy to avoid blind drug use should be advocated.As an efficient,fast and costeffective technical means,high-throughput in vitro drug sensitivity detection based on PDC model constructs a powerful platform for preclinical drug discovery of oral squamous cell carcinoma.Receiving high-throughput in vitro drug sensitivity test before drug treatment can quickly evaluate the individual sensitivity of tumor drugs,with high reliability.It can provide reference for the formulation of individualized drug regimen for oral squamous cell carcinoma,and may promote the implementation of individualized treatment for oral squamous cell carcinoma.