Patient-derived Organoids and Mini-PDX for Predicting MET-mutated Lung Cancer Patient Clinical Therapeutic Response

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Sep 27

PMID 39328538

Authors

Meng Jiang

Rongfu Tu

Yiwen Pan

Yuxin Cui

Xin Qi

Hongyu Qin

Lijuan Liu

Xiaorui Wang

Ying Xue

Yao Xu

Ziyang Peng

Chengsheng Zhang

Jin Yang

Affiliations

Soon will be listed here.

Abstract

Lung cancer as a molecularly and histologically high heterogonous disease, there is an urgent need to predict lung cancer patients' responses to anti-cancer treatment, and patient-derived organoids (PDOs) have been recognized as a valuable platform for preclinical drug screening. In this study, we successfully established 26 PDO lines from various subtypes of lung cancers including benign tumor, adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, large-cell carcinoma, and small-cell carcinoma. These PDOs were shown to retain the major genomic and histological characteristics of primary tumors and remain stable during long-term culture. With the help of targeted genomic sequencing, we found that lung cancer that harbors MET mutation is selectively sensitive to afatinib, and a combination of afatinib and gemcitabine induced synthetic lethality in PDO and mini-PDX models. In summary, our findings demonstrate the potential of PDO in predicting lung cancer drug response, and reveal a promising strategy for MET mutant lung cancer treatment.

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