Breakthroughs in liver cancer screening and treatment

Primary liver cancer is one of the deadliest cancers globally, with a five-year survival rate of 20%.¹ It is also one of the most quickly increasing types of cancer in the U.S,² more than tripling since 1980.¹ The disease used to be most commonly diagnosed in older people and those with chronic hepatitis infections. Today it is being seen more often in younger and uninfected people, due in part to lifestyle challenges that cause obesity, diabetes, and increased exposure to environmental toxins and pollutants.

Because liver cancer usually progresses silently, without noticeable symptoms in its early stages, it is often not diagnosed until an advanced stage when treatment options are limited. Early detection is key to battling this disease. Available screenings for high-risk individuals are not always reliable, and while treatments for advanced disease may help keep symptoms or cancer growth at bay, they cannot cure the disease.

With such a high mortality rate and increase in prevalence, new screenings and treatments are more important than ever. Fortunately, there are exciting developments on the forefront that offer hope.

Early Detection: On the forefront

People at high risk are advised to undergo regular monitoring. Risk factors include hepatitis B or C, obesity, excess alcohol consumption, non-alcoholic fatty liver disease, exposure to aflatoxins (a toxin found in moldy peanuts or grains), cirrhosis, type 2 diabetes, and some auto-immune and hereditary/inherited diseases and conditions.^2,3,4 Screenings for high-risk individuals currently include blood tests that look for alpha-fetoprotein (AFP) a protein that can be measured in the blood of patients with liver cancer, and ultrasounds every six months. These tests, however, are not always accurate in their detection of early stage liver cancer.^5,6

Imaging
Improved screening methods have the potential to save lives by detecting the disease at earlier, more treatable stages. On the forefront is the use of CT scans and MRIs in place of ultrasounds, as they are more sensitive to developing cancers and able to show more detail and higher resolution images. Specifically, abbreviated MRI protocols that have been tailored for identification of liver cancer have shown promise in more accurate early detection for those at high risk.^6,7

New blood tests
Several new blood tests using biomarkers are being studied to detect liver cancer earlier than AFP.⁸ The development of fragmentomics, a new type of technology that analyzes bits of DNA, is also very promising. Both healthy and cancerous cells shed pieces of their DNA into the bloodstream. By studying the patterns in the amount and size of DNA fragments, fragmentomics can identify the cancer cells that discarded them.⁹ In a National Cancer Institute (NCI) funded study, preliminary data showed the blood test accurately detected liver cancer in people with early stages of the disease.⁹

Current treatment options for liver cancer are often limited and may include surgery, radiation, chemotherapy, targeted therapies, and immunotherapies that act on specific proteins in cancer cells or their surrounding environments. These treatments may not be effective for all patients, and in later stages are palliative, not curative.

Advancements in cancer research have led to more personalized treatment approaches, where therapies are tailored to the unique genetic and molecular characteristics of an individual’s tumor. This personalized approach, called precision oncology, shows promise in improving treatment outcomes. In 2022 alone, significant progress was made in many aspects of liver cancer research which emphasized the importance of precision oncology.¹⁰ For example, several studies identified possible biomarkers for new immunotherapies; others focused on the development of targeted therapies, combination therapies, and potential gene therapies^11,12 to address a tumor’s specific characteristics.

A key component of precision oncology is molecular profiling, where the molecular characteristics of the tumor cells are identified to help determine which treatments might be most effective. In a clinical study, 86% of samples from patients with liver cancer that were tested with the Oncotype MAP Pan-Cancer Tissue molecular profiling test had results that could be used to guide treatment decisions.¹³ Molecular profiling is also being used to study ways to predict if the cancer will come back by testing the liver cells from a surgery sample.⁸

Breakthroughs in screening, characterization, and treatments for liver cancer offer the potential to increase survival rates, and while some still need to be validated and confirmed in larger studies, they take huge strides in addressing major challenges of the disease.

References

1. Liver Cancer – Statistics. Cancer.Net https://www.cancer.net/cancer-types/liver-cancer/statistics (2012).
2. Liver Cancer. MD Anderson Cancer Center https://www.mdanderson.org/cancer-types/liver-cancer.html.
3. Liver cancer – Symptoms and causes. Mayo Clinic https://www.mayoclinic.org/diseases-conditions/liver-cancer/symptoms-causes/syc-20353659.
4. Liver Cancer Risk Factors | Risk of Liver Cancer. https://www.cancer.org/cancer/types/liver-cancer/causes-risks-prevention/risk-factors.html.
5. Can Liver Cancer Be Found Early? https://www.cancer.org/cancer/types/liver-cancer/detection-diagnosis-staging/detection.html.
6. VA launches largest ever liver cancer screening study – VA News. https://news.va.gov/113501/va-launches-largest-liver-cancer-screening/ (2022).
7. Gupta, P. et al. Abbreviated MRI for hepatocellular carcinoma screening: A systematic review and meta-analysis. J. Hepatol. 75, 108–119 (2021).
8. What’s New in Liver Cancer Research? https://www.cancer.org/cancer/types/liver-cancer/about/new-research.html.
9. Blood Test Uses Fragmentomics to Detect Liver Cancer – NCI. https://www.cancer.gov/news-events/cancer-currents-blog/2023/liver-cancer-liquid-biopsy-fragmentomics (2023).
10. Liao, W., Calvisi, D. F. & Chen, X. Year in review: Liver cancer research in 2022: tumor microenvironment takes the central stage. Hepatol. Commun. 7, e0074 (2023).
11. News. Gene therapy study identifies potential new treatment for liver cancer. news https://health.ucdavis.edu/news/headlines/gene-therapy-study-identifies-potential-new-treatment-for-liver-cancer/2023/08.
12. Hu, Y. et al. miR-22 gene therapy treats HCC by promoting anti-tumor immunity and enhancing metabolism. Mol. Ther. 31, 1829–1845 (2023).
13. Kundranda, M. N. et al. Molecular profiling to identify potential therapeutic targets in hepatocellular carcinoma. J. Clin. Oncol. 40, 471–471 (2022).