Establishment and Preclinical Application of Conditional Reprogramming Culture System for Laryngeal and Hypopharyngeal Carcinoma release_w6gfyyryabhfvlhs6e4ypkcbie

Abstract

<jats:title>Abstract</jats:title> <jats:bold>Purpose</jats:bold> Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to their anatomic location and highly variable therapeutic responses. We aim to establish a new in vitro model for LHSCC based on conditional reprogramming (CR), a novel cell-culture technique, and investigate its potential value on personalized cancer therapies. <jats:bold>Methods</jats:bold> Primary LHSCC cells were isolated from tumor specimens and cultured under CR conditions. The characteristics and malignant potential of cells were evaluated by histological staining, whole-exome sequencing and heterotransplantation. The responses of CR tumor cells to anticancer drugs and radiotherapy were tested using cell proliferation assay. CR cells could form xenografts and organoids, which were used for drug testing respectively. Clinical responses for certain patients were also compared with <jats:italic>in vitro</jats:italic> responses. <jats:bold>Results</jats:bold> A panel of 28 human LHSCC CR cells were established from 50 tumor tissues. They retain tumorigenic potential upon xenotransplantation and recapitulate molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected <jats:italic>in vitro</jats:italic>. CR cells can be transformed to xenograft and organoid, shared comparable drug responses. The clinical drug responses were consistent with <jats:italic>in vitro </jats:italic>drug responses. <jats:bold>Conclusions</jats:bold> The patient-derived CR cell model could promisingly be utilized in clinical decision-making and assist in the selection of personalized therapies for LHSCC.
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