Target immune components to circumvent sorafenib resistance in hepatocellular carcinoma
Shuhua Wei1, Fenghua Wei2, Mengyuan Li1
1Department of Radiation Oncology, Peking University Third Hospital, Beijing, PR China.
Abstract:
Sorafenib, a multi-kinase inhibitor, has been approved for cancer treatment for decades, especially hepatocellular carcinoma (HCC). Although sorafenib produced substantial clinical benefits in the initial stage, a large proportion of cancer patients acquired drug resistance in subsequent treatment, which always disturbs clinical physicians. Cumulative evidence unraveled the underlying mechanism of sorafenib, but few reports focused on the role of immune subpopulations, since the immunological rationale of sorafenib resistance has not yet been defined. Here, we reviewed the immunoregulatory effects of sorafenib on the tumor microenvironment and emphasized the potential immunological mechanisms of therapeutic resistance to sorafenib. Moreover, we also summarized the clinical outcomes and ongoing trials in combination of sorafenib with immunotherapy, highlighted the immunotherapeutic strategies to improve sorafenib efficacy, and put forward several prospective questions aimed at guiding future research in overcoming sorafenib resistance in HCC.
Insights
Sorafenib resistance in liver cancer (HCC) is a major challenge. This review explores the immune system's role in sorafenib resistance and discusses immunotherapy combinations to improve treatment outcomes.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Sorafenib is a key treatment for hepatocellular carcinoma (HCC), but drug resistance limits its long-term efficacy.
- Mechanisms of sorafenib resistance are not fully understood, particularly the role of immune cells.
Purpose of the Study:
- To review the immunoregulatory effects of sorafenib.
- To define the immunological mechanisms underlying sorafenib resistance in HCC.
- To explore combination strategies of sorafenib with immunotherapy.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of immunoregulatory effects of sorafenib on the tumor microenvironment.
- Summary of clinical outcomes and ongoing trials for sorafenib-immunotherapy combinations.
Main Results:
- Sorafenib influences various immune cell subpopulations within the tumor microenvironment.
- Immune evasion and dysregulation are key contributors to sorafenib resistance.
- Combination therapies show promise in overcoming resistance and enhancing efficacy.
Conclusions:
- Understanding the immunological basis of sorafenib resistance is crucial for developing effective treatments.
- Combining sorafenib with immunotherapy offers a promising strategy to improve outcomes in HCC patients.
- Further research is needed to optimize these combination strategies and overcome resistance.
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