Patient-derived organoids assist personalized treatment for a patient with multiple metastatic neuroendocrine carcinoma of the cervix

Abstract

SUMMARYNeuroendocrine carcinoma of the cervix (NECC) is a rare subtype of cervical cancer with rapid metastasis. Lack of treatment regimens for metastatic NECC highlights the need for preclinical models and personalized treatment. Here, we established two patient-derived NECC organoid lines from lung metastases from the same patient, one of which was drug-free and the other exhibited tolerance to carboplatin plus etoposide (EP). The two organoids recapitulated the histopathology and genomic spectrum of the original tumors. Whole-genome sequencing revealed genomic structural variations (SVs), including HPV16 infection, NEUROD2, and ERBB2 amplification. The sensitivity phenotype of organoids to ERBB2 inhibitors coincides with the genomic features of ERBB2 amplification. In addition, the patient after relapse responded well to the paclitaxel plus carboplatin (TC) regimen as recommended by organoid drug screening, underscoring the utility of organoids as preclinical models. We first provide two NECC organoids of lung metastases with comprehensive molecular characteristics as valuable resources for this rare cancer and give a typical application for personalized treatment based on organoids.