Related Experiment Video
Updated: Nov 21, 2025
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
The New Immuno-Oncology-Based Therapies and Their Perspectives in Hepatocellular Carcinoma
1Centre de Recherche sur le Cancer de Lyon (CRCL), Hepatology and Gastroenterology Unit, Croix-Rousse Hospital, Hospices Civils de Lyon and INSERM U1052, Epigenetics and Epigenomics of Hepatocellular Carcinoma (EpiHep), 69004 Lyon, France.
Abstract:
Hepatocellular carcinoma is a poor prognosis tumor. Systemic therapies are frequently used due to frequent recurrences after surgical or radiologic treatments. Anti-angiogenic tyrosine kinase inhibitors have shown efficacy in monotherapy, but with very low rates of long survival and exceptional recovery. Immuno-oncology based on immune checkpoint inhibitors has revolutionized the systemic therapies since showing long survival rates without any tumor progression or recurrence for some patients in partial or complete response, and possibly for some patients in stable disease. However, the rate of responders under immuno-oncology monotherapy is too low to increase significantly the median overall survival of the treated patients. The immuno-oncology-based combinations with different types of immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 inhibitors such as nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, tremelimumab), or the association of immune checkpoint inhibitors plus anti-angiogenic agents (bevacizumab, lenvatinib, cabozantinib), have led to a breakthrough in the treatment of hepatocellular carcinoma. Indeed, the first phase-3 trial, combining atezolizumab with bevacizumab, has dramatically changed the outcome of patients. Data from several other types of combinations assessed in phase-3 trials are pending, and if positive, will drastically arm the physicians to efficiently treat the patients, and disrupt the current algorithm of hepatocellular carcinoma treatment.
Insights
Combining immune checkpoint inhibitors with anti-angiogenic agents represents a breakthrough in hepatocellular carcinoma treatment. These novel systemic therapies offer improved outcomes for patients with this poor prognosis cancer.
Area of Science:
- Hepatocellular carcinoma (HCC) research
- Cancer immunotherapy
- Translational oncology
Background:
- Hepatocellular carcinoma (HCC) is an aggressive cancer with frequent recurrence after primary treatments.
- Systemic therapies are crucial for managing advanced HCC, but monotherapies have limited efficacy.
- Anti-angiogenic tyrosine kinase inhibitors show modest benefits, while immune checkpoint inhibitors (ICIs) offer durable responses in a subset of patients.
Purpose of the Study:
- To review the advancements in systemic therapies for hepatocellular carcinoma (HCC).
- To highlight the efficacy of combination strategies involving immune checkpoint inhibitors (ICIs) and anti-angiogenic agents.
- To discuss the potential impact of ongoing clinical trials on HCC treatment paradigms.
Main Methods:
- Review of current literature on systemic therapies for HCC.
- Analysis of clinical trial data for immune checkpoint inhibitors (ICIs) and anti-angiogenic agents.
- Evaluation of combination therapies in phase-3 trials for HCC.
Main Results:
- Immune checkpoint inhibitors (ICIs) have revolutionized HCC treatment, offering long-term survival for some patients.
- Combination therapies, particularly atezolizumab plus bevacizumab, have demonstrated significant improvements in patient outcomes.
- Ongoing phase-3 trials are investigating further combinations, promising enhanced treatment options.
Conclusions:
- Combination strategies involving immune checkpoint inhibitors (ICIs) and anti-angiogenic agents represent a breakthrough in HCC management.
- These novel approaches are poised to significantly alter the treatment landscape for hepatocellular carcinoma.
- Further clinical trial data will refine and expand therapeutic options for HCC patients.
Related Concept Videos
01:27Tumor Immunotherapy
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...