Removing the breeding ground for tumors

FAU researchers present new approach in the fight against liver metastases

An interdisciplinary research team from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and the University Hospital Erlangen is pursuing a new tactic in the fight against liver cancer. Instead of targeting the cancer cells as before, they are focusing on the liver environment. The basis of the new approach is a protein molecule produced by the liver, which makes the liver an attractive implantation target for disseminated cancer cells. The researchers have presented their novel therapeutic approach for the treatment of liver metastases in Proceedings of the National Academy of Sciences (PNAS).

A communication channel between cancer cells and the liver

The research focuses on the NPY-Y5R signaling axis. NPY is produced in the liver and mediates positive signals for cell migration, cell growth and cell survival. This establishes a stimulating microenvironment in the liver niche. Cancer cells in turn produce a "sensor" for NPY on their surface - the receptor Y5R - which enables them to use the fertile environment to become established in the liver. If this communication is specifically disrupted, the cancer cells find it much more difficult to gain a foothold in the liver.

"We address the niche, not the tumor"

"Forms of therapy that directly target the tumor often fail due to problems such as poor accessibility of the cancer cells, insufficient specificity, strong unexpected side effects or rapid development of resistance," explains Dr. Laura Wormser from the Department of Biochemistry and Molecular Medicine and first author of the publication. In a promising approach, the research group therefore targeted the liver niche instead of the cancer cells. In their study, the researchers were able to disrupt the communication between the tumor cell and the liver niche in preclinical models and thus successfully limit liver metastasis. "We show that the 'language' of the liver can be changed in such a way that metastases do not take root in the first place," says Laura Wormser. "The step away from the tumor cell to the organ niche opens up therapeutic options that were previously unattainable," adds Dr. Peter Dietrich, head of the study. "This deprives the tumor of the 'breeding ground' it needs to colonize and grow in the liver."

From experimental findings to clinical application

Metastases are the main cause of cancer-related deaths - and the liver is particularly frequently affected, including in black skin cancer, colon, pancreatic, stomach and breast cancer patients. If the niche is influenced, the colonization and spread of tumour cells can be made significantly more difficult. "The next steps include fine-tuning the form of therapy, safety tests and the path to early clinical application," says Dr. Laura Wormser. "But there is still a long way to go before it is ready for use."

Directly to the study:
https://www.pnas.org/doi/10.1073/pnas.2518418122