Abstract

Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to highly variable therapeutic responses. By establishing an in vitro model for LHSCC based on conditional reprogramming (CR), a cell-culture technique, we aim to investigate its potential value on personalized cancer therapies. Herein, a panel of 28 human LHSCC CR cells were established from 50 tumor tissues using the CR method. They retained tumorigenic potential upon xenotransplantation and recapitulated molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells could be transformed to xenograft and organoid, and they shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Collectively, the patient-derived CR cell model could promisingly be utilized in clinical decision-making and assisted in the selection of personalized therapies for LHSCC.

Highlights

  • Malignant tumors arising from the epithelium of the larynx and hypopharynx are predominantly squamous cell carcinomas, constituting the most frequent malignancies of head and neck squamous cell carcinomas (HNSCC)

  • By establishing an in vitro model for laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) based on conditional reprogramming (CR), a cell-culture technique, we aim to investigate its potential value on personalized cancer therapies

  • Conditional reprogramming (CR) has been documented by two American National Cancer Institute programs: patient-derived cancer model repository (PDMR) and human cancer model initiatives (HCMI)

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Summary

Introduction

Malignant tumors arising from the epithelium of the larynx and hypopharynx are predominantly squamous cell carcinomas, constituting the most frequent malignancies of head and neck squamous cell carcinomas (HNSCC). Insensitive to radiotherapy or chemotherapy frequently occurs, one of the significant causes of tumor recurrence, and is associated with poor outcome. The reported advantages of CR include high success rate, exponential growth, genotype stability, and ease of manipulation. These characteristics enabled CR as an exceptional in vitro model compared with the others, such as patient-derived xenotransplantation (PDX) and organoids. Owing to these advantages, CR has been documented by two American National Cancer Institute programs: patient-derived cancer model repository (PDMR) and human cancer model initiatives (HCMI)

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