Clinical and molecular profiles of Hepatocellular Carcinoma (HCC) treated with combination immunotherapy

Liver cancer, which is the abnormal and uncontrolled growth of cells in the liver, is a common and serious health concern globally, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related deaths. One prominent form of liver cancer is hepatocellular (main cells of the liver) carcinoma (HCC), representing over 80% of liver cancer cases and contributing significantly to global cancer mortality.

Several key factors increase the risk of HCC. These factors include chronic infection with hepatitis B or C viruses (infections of the liver that are transmitted through blood), excessive alcohol consumption, exposure to aflatoxin (a toxin produced by certain molds found in food), the presence of non-alcoholic fatty liver disease (fat accumulation mainly due to overweight/obesity, diabetes, and lipid disorders), and genetic factors. The interplay of these risk factors adds complexity to the disease, leading to diverse clinical presentations and varied responses to treatment.

There is an essential need for the development of effective medical therapies for HCC patients, especially for advanced-stage liver cancer. Recent progress in clinical trials for HCC has focused on exploring innovative therapeutic approaches based on immuno-oncology (treatment that focuses on using the body's own immune system to fight cancer) that will prolong the patients’ lives and improve their quality of life. A significant frontier in HCC research involves identifying and validating biomarkers, which are characteristics used as indicators of biological processes. These biomarkers play a crucial role in early detection of HCC and predicting how HCC patients respond to treatments. This groundbreaking work is advancing the field of HCC treatment towards personalized medicine, which means selecting appropriate treatment for individual patients based on their specific biomarkers.
However, existing clinical trials primarily emphasize the assessment of treatment effectiveness. Furthermore, there is limited knowledge on the causal relationships between clinical features, biomarkers, and treatment efficacy. Therefore, we aim to evaluate the impact of clinical characteristics and molecular biomarkers on the treatment effectiveness of HCC patients who had received combination immunotherapy, by using in-depth and comprehensive secondary data analysis on clinical trials. Combination immunotherapy involves treatments like radiation being used together with immunotherapy, which can enhance the effectiveness compared to using a single treatment alone. Identifying the clinical and molecular profiles of HCC patients treated with combination immunotherapy is crucial because understanding how these therapies work together and pinpointing key biomarkers can lead to better, more effective treatments for patients.