Mini-tumors identify liver cancer drug combination in mice

A collection of 35 living, three-dimensional liver-cancer mini-tumors has given researchers at the University of Basel a testing ground for treatments across different forms of the disease. In mice carrying tumors derived from those organoids, a combination of regorafenib, selinexor and ixazomib slowed tumor growth more effectively than regorafenib alone, without significant additional toxicity in the studied model.

The team, led by Professor Markus Heim and Dr. Sandro Nuciforo, focused on hepatocellular carcinoma, the most common form of liver cancer. Its tumors can differ according to the cause of the disease and the genetic changes in cancer cells, helping explain why immunotherapies and other drugs work for some patients but not all.

The organoids—three-dimensional structures made from living cancer cells—retain key characteristics of the tumors they represent. Many were grown from small samples taken during diagnostic needle biopsies, including advanced tumors that were underrepresented in earlier organoid collections. The researchers first ran an automated screen of 1,642 compounds on four selected organoids, then tested promising candidates across a larger selection.

Rather than target one vulnerability, the researchers combined drugs with different mechanisms of action. Several two- and three-drug combinations performed better across different tumor organoids than individual medicines. Some three-drug combinations also had a markedly weaker effect on non-tumor liver organoids, suggesting more selective targeting in these models.

Concretely, the collection gives researchers a way to compare treatments against a broader range of liver tumors before they are considered for patients. It does not change clinical care yet. Organoids do not fully capture blood vessels, immune cells and other components around a tumor, and the triple therapy still needs further study before it can be used in patients.