Patient-Derived Lung Cancer Organoids for Precision Oncology: A Comprehensive Analysis

We aimed to comprehensively assess the accuracy of patient-derived organoids to recapitulate the genomic features of patient tumors, and to quantify the reliability of patient-derived organoid-based drug screening, by pooling the available evidence and the validation using our patient-derived lung cancer organoids (LCOs).

A comprehensive online search was conducted to identify eligible studies. A total of 20 LCOs harvested from surgical samples were also established as our internal validation cohort, with whole-exome sequencing and transcriptomic sequencing performed, respectively. Pooled concordance in genetic profiles between LCOs and original tumors was calculated, along with the overall accuracy of LCOs for drug profiling.

The pooled concordance in mutational landscape between LCOs and original tumors reached 74% (95% confidence interval [CI]: 61%-84%) in overall populations without heterogeneity (I ² = 0%, p = 0.918), and that in gene expression achieved 70% (95% CI: 51%-84%; I ² = 8.5%, p = 0.437). Subgroup analyses of our internal LCOs by morphologic patterns suggested that LCOs retained genetic fidelity regardless of intratumoral histologic heterogeneity and pathologic features. The accuracy of LCOs for predicting drug sensitivity achieved 90.7% (95% CI: 77.4%-9.2%) in the pooled populations with mild heterogeneity (I ² = 30.2%, p = 0.231).

Our study indicates that LCOs can stably recapitulate the genomic features of patient tumors irrespective of histologic heterogeneity and be a promising precision medicine tool for anticancer drug screening or for predicting drug responses.