A multicenter research team has successfully demonstrated that patient-derived organoids (PDOs) can effectively predict chemotherapy responses in patients with esophageal squamous cell carcinoma (ESCC), marking a significant advancement in personalized cancer treatment.
The comprehensive study, conducted across multiple institutions including Nanjing Drum Tower Hospital and Peking University Cancer Hospital, analyzed 55 patient samples to develop three-dimensional organoid cultures. The research team achieved a 62% success rate in establishing viable organoid cultures, with 30 organoid lines ultimately undergoing detailed drug sensitivity testing.
These laboratory-grown miniature versions of patient tumors showed remarkable fidelity to their source tissues, maintaining key architectural features and molecular markers characteristic of ESCC. The organoids preserved essential markers including CK5/6, p53, KLF5, and SOX2, confirming their biological relevance as experimental models.
In a crucial validation of the technology's clinical utility, the researchers tested the organoids against standard chemotherapy regimens, including cisplatin alone and combination therapies such as paclitaxel plus cisplatin (TP), vinorelbine plus cisplatin (NP), and 5-fluorouracil plus cisplatin (FP). The results revealed distinct response patterns among different patient samples, highlighting the heterogeneous nature of ESCC.
"The correlation between organoid drug responses and patient outcomes was particularly striking," notes the research team. Among the 12 evaluable patients who received chemotherapy, 10 showed consistency between their clinical responses and the predictions made by their corresponding organoids – an impressive 83.33% concordance rate.
The study revealed that patients whose organoids showed sensitivity to the TP regimen demonstrated significantly better progression-free survival compared to those with resistant organoids. This finding suggests that PDO testing could serve as a valuable tool for treatment stratification.
Notably, the timeframe for obtaining drug assay results – approximately 2-8 weeks – aligns well with clinical decision-making windows, making the technology practically applicable in real-world settings. This timing allows oncologists to potentially adjust treatment strategies based on organoid testing results before initiating or modifying chemotherapy regimens.
The research also included detailed case studies that further validated the technology's predictive power. In one notable example, a patient whose organoids showed resistance to TP treatment experienced disease progression within six months, while patients with sensitive organoids achieved sustained clinical responses.
These findings represent a significant step toward more personalized treatment approaches in ESCC, potentially helping clinicians avoid ineffective treatments and optimize therapeutic strategies for individual patients. The technology could particularly benefit patients in advanced stages of ESCC, where choosing the most effective first-line treatment is crucial.
