Innovative Lab-Grown Tumor Miniatures Bring New Hope for Esophageal Cancer Treatment

Esophageal cancer remains a significant global health challenge, ranking as the seventh most common cancer case and sixth leading cause of cancer-related deaths worldwide. In regions like East Asia and Japan, over 90% of these cases are diagnosed as esophageal squamous cell carcinoma (ESCC). One of the major hurdles in effective treatment is the high rate of cancer recurrence, with only about 55% to 63.6% of patients remaining cancer-free five years post-treatment.

To address the urgent need for more effective therapies targeting chemotherapy-resistant ESCC, a research team led by Professor Toshiaki Ohteki and former Associate Professor Taku Sato from the Institute of Science Tokyo developed a groundbreaking library of patient-derived organoids. These miniaturized, three-dimensional cancer models are grown in the laboratory from tumor samples obtained directly from patients. They allow researchers to investigate the mechanisms behind drug resistance and to screen potential therapeutic options more accurately than traditional models.

Published in the journal Communications Biology on April 1, 2025, the study involved collaboration with experts from Keio University and Tokyo Metropolitan Cancer and Infectious Diseases Center. Unlike artificial models created by exposing cancer cell lines repeatedly to chemotherapy, these organoids more faithfully mimic the traits of original tumors, including common genetic mutations such as TP53, and display features like nuclear p53 accumulation and rapid cell proliferation.

The team cultivated organoids from tumor samples of 24 diverse ESCC patients. When transplanted into immunodeficient mice, these organoids formed tumors that closely resembled the patients’ original cancers, confirming their validity as models for studying the disease.

The researchers tested the response of these organoids to standard chemotherapy drugs cisplatin and 5-fluorouracil (CF). While most organoids (71%) responded to treatment, a notable 29% exhibited resistance. Further analysis revealed that resistant organoids had increased activity in the NRF2 pathway, which enhances the cell’s antioxidant defenses and contributes to drug resistance through overexpression of genes like ALDH3A1, SPP1, and TXNRD1.

This discovery underscores the importance of identifying biomarkers for early prediction of chemotherapy resistance. Professor Sato emphasized that roughly 28% of ESCC patients do not respond well to preoperative chemotherapy, highlighting the necessity for personalized treatment strategies.

The organoid library also served as a platform to assess new drugs. Notably, fedratinib demonstrated superior efficacy compared to standard therapies in inhibiting the growth of resistant organoids. Interestingly, its anti-tumor activity appeared independent of the NRF2 pathway, likely involving the inhibition of BRD4, a critical protein in cancer cell proliferation.

These findings showcase the transformative potential of organoid technology in cancer research. By enabling precise modeling of chemotherapy-resistant tumors, this approach paves the way for developing targeted therapies, offering renewed hope for patients with this aggressive disease.

Source: https://medicalxpress.com/news/2025-06-lab-grown-patient-tumor-miniatures.html