Patient-derived tumor organoids—3D tissue cultures derived from tumor tissue samples—could be used to predict the most suitable treatment for patients with biliary tract cancer, suggests research presented at Digestive Disease Week 2023 in Chicago.
Biliary tract cancers are relatively uncommon (around 8000 people in the United States are diagnosed with bile duct cancer per year) but typically have a poor prognosis because they are frequently diagnosed at a late stage. The 5-year survival rate is around 10%.1
At the time of diagnosis, the disease is often too advanced for patients to be eligible for surgery, leaving chemotherapy as the only option. However, patients show variable responses to chemotherapy and at present there is no effective way to predict outcomes.
Tumor organoids are a valuable tool for studying cancer biology and developing personalized cancer treatments because they mimic the characteristics of the tumors they are derived from, including key genetic and phenotypic features.
The 3D cell cultures have already been established for a number of cancer types, including breast, colon, lung, and bladder cancer. In the current analysis, Xiaoxue Ren, a PhD student from The First Affiliated Hospital of Sun Yat-Sen University Department of Oncology in Guangzhou, China, and colleagues investigated whether patient-derived organoids can be used for personalized drug screening among patients with biliary tract cancer.
She reported that 61 biliary tract cancer organoids were created from the 82 tumor samples they collected, giving a success rate of 74.4%. Immunohistochemistry staining showed that the organoids had similar histological characteristics to their corresponding primary tumor tissues, and Ren noted that the organoids formed more easily when they were derived from tumor tissues with enhanced stemness, which indicates the cells capability for self-renewal and differentiation, and proliferation-related gene expression.
Following the creation of the organoids, which takes around 1–2 weeks, the researchers applied different chemotherapeutic drugs (gemcitabine, cisplatin, 5-fluoruracil, oxaliplatin, irinotecan, mitomycin C, and paclitaxel) to investigate how the tumors might respond in vivo.
They observed a wide range of responses to the treatments, and the findings were validated in mouse models that were given xenografts of tissue from the organoids.
Ren and team then compared their findings with data from patients who had experienced a clinical response to chemotherapy. They found that the treatment response in the organoids matched that in the patient in 12 (92.3%) out of 13 cases, which Ren said indicates “the feasibility of drug screening using patient-derived organoids.”
The investigators also looked at gene expression signatures within the organoids and identified gene-based panels to predict chemotherapy responses. They found that these panels predicted the response to 5-fluoruracil, gemcitabine, and cisplatin with 90.7%, 86.4%, and 82.1% accuracy, respectively.
Ren told Inside Precision Medicine that these panels could be particularly useful for the approximate 30% of patients for whom it is not possible to establish organoid culture.
Next, she plans to design a prospective clinical trial using organoids to predict patient response and will also investigate their utility with immune checkpoint inhibitors.
Ren concluded: “Organoids could be a good clinical decision support tool for the biliary tract cancer patients and their doctors.”
References:
- https://www.cancer.net/cancer-types/bile-duct-cancer-cholangiocarcinoma/statistics
