Liver cancer is a challenging disease to treat due to the significant variation in tumors between patients. Researchers at the University of Basel have developed a collection of mini-tumors, known as organoids, to systematically search for new treatment options. These organoids are three-dimensional structures composed of living cancer cells that retain key characteristics of the original tumor.
Unlike earlier studies, this group included many organoids created from biopsy samples taken during routine diagnostics, covering advanced-stage tumors that had rarely been studied before.
The research group screened 1,642 substances, including existing cancer treatments, experimental agents, and medications approved for unrelated conditions, against four representative liver cancer organoids. A number of these compounds showed strong tumor-suppressing properties, making them potential candidates for liver cancer therapy. The team then explored multi-drug regimens with varied mechanisms to address tumors whose weaknesses differ between patients.
Certain two- and three-drug combinations outperformed single treatments against diverse tumor organoids. Notably, some three-drug mixes had a significantly reduced impact on healthy liver organoids compared to cancerous ones, indicating a more precise attack on malignant cells. The researchers focused on a specific trio, regorafenib, selinexor, and ixazomib, which proved more effective than regorafenib alone at slowing tumor progression in mice implanted with patient-derived organoids.
Further studies are needed before this combination can be used in patients. Organoids only incompletely capture blood vessels, immune cells, and other components of a tumor’s microenvironment. However, this study demonstrates how a diverse collection of organoids derived from patient samples can be used to systematically test drugs and develop combination therapies that are effective despite major differences between tumors. As hepatocellular carcinoma is a complex disease, the use of organoids may help identify new treatment options.
The researchers’ findings are published in Cell Reports, and their study provides new insights into the potential use of approved drugs and new drug combinations for treating liver cancer. The collection of organoids established by the researchers reflects different stages of the disease, as well as liver tumors with various causes, allowing for the testing of which drugs are effective despite significant biological differences between tumors.
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