Unleashing the efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma: factors, strategies, and ongoing trials

Front Pharmacol. 2023 Aug 31:14:1261575. doi: 10.3389/fphar.2023.1261575. eCollection 2023.

Abstract

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer, representing approximately 85% of cases. The diagnosis is often made in the middle and late stages, necessitating systemic treatment as the primary therapeutic option. Despite sorafenib being the established standard of care for advanced HCC in the past decade, the efficacy of systemic therapy remains unsatisfactory, highlighting the need for novel treatment modalities. Recent breakthroughs in immunotherapy have shown promise in HCC treatment, particularly with immune checkpoint inhibitors (ICIs). However, the response rate to ICIs is currently limited to approximately 15%-20% of HCC patients. Recently, ICIs demonstrated greater efficacy in "hot" tumors, highlighting the urgency to devise more effective approaches to transform "cold" tumors into "hot" tumors, thereby enhancing the therapeutic potential of ICIs. This review presented an updated summary of the factors influencing the effectiveness of immunotherapy in HCC treatment, identified potential combination therapies that may improve patient response rates to ICIs, and offered an overview of ongoing clinical trials focusing on ICI-based combination therapy.

Keywords: clinical trial; combination therapy; hepatocellular carcinoma; immune checkpoint inhibitors; preclinical study.

Publication types

  • Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative, NMRC/OFLCG/003/2018, Cancer ImmunoTherapy Imaging (CITI) Programme: Precision Immnue Cell Imaging for Precision Cancer Immunotherapy (H18/01/a0/018) and Joint NCIS and NUS Cancer Program Seed Funding Grants (R713-009–272-733).