Researchers are testing more than 1,600 drug compounds to identify promising treatments for liver cancer

The team tested more than 1,600 drug compounds, which helped it identify drugs and therapeutic combinations that showed promising results in combating the disease.

Liver cancer is one of the most difficult cancers to treat due to the large differences between tumors from one patient to another. Tumors may differ in their biological characteristics and the genetic changes they carry, and the causes of their infection may differ, which makes their response to treatment vary.

To address this diversity, the researchers created a set of 35 tumor organoid lines representing hepatocellular carcinoma, the most common type of liver cancer. These organoids are composed of living cancer cells in three-dimensional structures that maintain some basic characteristics of the original tumor.

The advantage of this model is that a number of organelles were developed from small samples taken during diagnostic needle biopsies, which allowed the representation of advanced tumors that were not sufficiently present in previous organelle sets.

Sandro Nuciforo, the first author of the study, said that the group represents different stages of the disease and tumors with diverse causes, which allows testing the effectiveness of drugs in light of the biological differences between tumors.

1642 compounds tested

The researchers began with an automated screening of 1,642 compounds on four selected organelles. The list included cancer drugs, experimental compounds, and drugs approved to treat other diseases. They then tested compounds that showed promising results on a wider range of organelles.

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Several drugs showed strong activity against tumors, before the team moved on to test combinations of drugs with different mechanisms of action. Some double and triple combinations showed greater effectiveness than drugs used alone, and some triple combinations appeared to affect cancer cells more selectively, with less effect on non-tumor liver organoids.

Markus Heim, who led the research team, said that combining drugs with different mechanisms may help maintain the effectiveness of treatment despite the differences in vulnerabilities between tumors.

Promising results in mice

The researchers tested one promising combination, combining regorafenib, selinexor and ixazomib, in mice bearing tumors derived from organoid models taken from patients.

Triple therapy slowed tumor growth more than regorafenib alone, without significant additional toxicity in the animal model.

However, the researchers stress that the results are still in the pre-clinical stage, and that more studies are needed before the combination is tested in patients. The organelles also do not fully mimic the environment surrounding the tumor, including blood vessels and immune cells.

The study suggests that patient-derived organoids can be used as a tool to systematically test a large number of drugs and help develop combination therapies that take into account the large differences between liver cancer tumors.