Research team identifies possible new targets for liver cancer therapy

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Liver tumors comprise an array of constantly changing pathophysiology biomolecules and cell types, a moving target that can evade effective treatment. But new research may have found a stable population of cells that could serve as a bull's eye for effective therapy.

Tumor cells arise, evolve and interact with surrounding tissue (the tumor microenvironment) in a swirl of activity that can mask the core molecular features of malignancy. Current research attempts to address this issue by zeroing in on the cellular dynamics of malignant cells and their communication networks that influence the immune system to hold back in attacking the cancer.

"Tumor evolution may be the main reason for therapeutic failure and consequent poor patient outcomes," the research group said in Nature Communications. The group was led by Xin Wei Wang of the National Cancer Institute’s Center for Cancer Research with collaborators including Michael Kelly of Frederick National Laboratory for Cancer Research Cancer Research Technology Program, and members of the Center for Cancer Research Single Cell Analysis Facility. 

Recent advances in single-cell analytic technologies made it possible to more accurately characterize the interaction between tumor cells and their surrounding microenvironment than was previously possible. Cancer growth requires mutated normal cells plus an altered tissue environment that helps a tumor survive and grow. The communication between the tumor and its microenvironment, unique to each tumor, presents a potential target for effective intervention. 

Using single-cell RNA sequencing analysis of tissue from seven liver cancer patients, the researchers identified two molecules from tumor tissue and two corresponding molecules from macrophages of the immune system whose interactions appear essential for tumor aggression. This may be a distinct if not unique molecular fingerprint of interactions between tumors and their microenvironment. They further validated their findings using data from 542 liver cancer patients. 

“Exploiting methods to disrupt these interactions could constitute a viable therapeutic strategy to target HCC [liver cancer] and stop tumor evolution, thereby improving treatment efficacy,” the researchers said. 

The study had its limitations, including the small number of patient samples and relatively short duration of clinical follow-up. But the scientific team is continuing to enroll patients for on-treatment studies and further research is underway. 

The National Cancer Institute says about 42,240 new liver cancer cases occurred in the United States last year with about 30,090 related fatalities. The overall five-year survival rate is 22 percent, indicating a need for new effective therapies. 

Preventative measures can also make a difference. A recent report in The Lancet said three of every five cases of liver cancer could be prevented by measures that address alcohol consumption, hepatitis, and obesity.