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A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Experimental drug treatments for hepatocellular carcinoma: clinical trial failures 2015 to 2021
Zachary J Brown1, D Brock Hewitt2, Timothy M Pawlik1,2
1Department of Internal Medicine, The Ohio State University Wexner Medical Center The James Cancer Hospital and Solove Research Institute, Columbus, Ohio, USA.
Introduction:
Hepatocellular carcinoma (HCC) is a major health problem worldwide with limited systemic therapy options. Since the approval of sorafenib in 2008, no systemic therapy has provided a sustained/robust/survival benefit for patients with advanced HCC until recently. Many initially promising therapies have been trialed, but survival outcomes remained stagnant. Knowledge concerning previous treatment failures may help inform future therapeutic approaches.
Area Covered:
This article reviews recent advances in the treatment of HCC. Despite some recent success, many systemic and locoregional therapies have failed to produce significant improvements in outcome. These treatment failures are examined and insight into pathways for future success are discussed.
Expert Opinion:
Combination atezolizumab and bevacizumab has changed the landscape of systemic treatment for patients with HCC when it became the first therapy after demonstrating improve outcomes over sorafenib. Clinical trials in patients with advanced HCC have inherent difficulty with challenges to determine if a patient's declining liver function is secondary to disease progression, worsening cirrhosis, or drug toxicity, which may skew results. As we gain more knowledge of underlying genetic alterations behind the pathophysiology of the development of HCC, molecular markers may be identified to assist in predicting which patients would respond to a specific therapy.
Insights
Hepatocellular carcinoma (HCC) treatment has advanced with combination atezolizumab and bevacizumab, offering improved outcomes. Understanding past treatment failures is crucial for developing future effective therapies for advanced HCC.
Area of Science:
- Hepatology
- Oncology
- Translational Medicine
Background:
- Hepatocellular carcinoma (HCC) presents a significant global health challenge with historically limited effective systemic therapies.
- Sorafenib, approved in 2008, was the primary systemic treatment for advanced HCC until recent advancements.
- Numerous therapeutic trials have failed to yield substantial survival benefits, highlighting the need for novel approaches.
Purpose of the Study:
- To review recent progress in HCC treatment strategies.
- To analyze the reasons behind previous treatment failures in HCC management.
- To discuss potential future directions for improving therapeutic outcomes in HCC.
Main Methods:
- Review of recent clinical trial data and therapeutic outcomes in advanced HCC.
- Analysis of systemic and locoregional therapies, including their successes and failures.
- Examination of the impact of combination atezolizumab and bevacizumab on HCC treatment landscape.
Main Results:
- Combination atezolizumab and bevacizumab represents a breakthrough, offering improved outcomes compared to sorafenib for advanced HCC.
- Challenges in clinical trials include differentiating disease progression, cirrhosis, and drug toxicity.
- Emerging knowledge of HCC's genetic underpinnings may lead to predictive molecular markers.
Conclusions:
- The combination of atezolizumab and bevacizumab has significantly altered the treatment paradigm for advanced HCC.
- Further research into predictive biomarkers is essential for personalized HCC therapy.
- Understanding past treatment failures is key to informing the development of more effective future HCC treatments.
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