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Updated: Aug 10, 2025
Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma
Published on: April 25, 2025
Clinical Utility of Comprehensive Genomic Profiling in Patients with Unresectable Hepatocellular Carcinoma
Shun Ishido1,2, Kaoru Tsuchiya1, Yoshihito Kano2,3
1Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-8610, Japan.
Abstract:
The molecular mechanism of hepatocellular carcinoma (HCC) is partially demonstrated. Moreover, in the patients receiving multiple molecular-targeted therapies, the gene alternations are still unknown. Six molecular-targeted therapies of unresectable HCC (uHCC) and comprehensive genomic profiling (CGP) have been approved in clinical practice. Hence, the utility of CGP in patients with uHCC treated with multiple molecular-targeted agents is investigated. The data of the patients with uHCC who received CGP tests were collected, retrospectively, between February 2021 and May 2022. Gene alterations detected by foundation testing, excluding variants of unknown significance, were reported in all nine patients. The samples for CGP were derived from liver tumor biopsy (n = 2), surgical specimens of bone metastases (n = 2), and blood (n = 5). The median number of systemic therapies was four. Seven patients were candidates eligible for clinical trials. One patient with a high tumor mutation burden (TMB) could receive pembrolizumab after CGP. This study presented genomic alternations after receiving multiple molecular-targeted therapies. However, further investigation needs to be conducted to develop personalized therapies and invent newer agents for treating HCC.
Insights
Comprehensive genomic profiling (CGP) identified gene alterations in patients with unresectable hepatocellular carcinoma (HCC) after multiple molecular-targeted therapies. This aids in understanding genomic changes for future personalized treatment strategies.
Area of Science:
- Oncology
- Genomics
- Hepatocellular Carcinoma Research
Background:
- The molecular mechanisms of hepatocellular carcinoma (HCC) are not fully understood.
- Gene alterations in patients with unresectable HCC (uHCC) undergoing multiple molecular-targeted therapies remain largely unknown.
- Six molecular-targeted therapies and comprehensive genomic profiling (CGP) are approved for clinical use in uHCC.
Purpose of the Study:
- To investigate the utility of CGP in patients with uHCC treated with multiple molecular-targeted agents.
- To identify genomic alterations in uHCC patients post-multiple therapies.
Main Methods:
- Retrospective collection of data from uHCC patients who underwent CGP between February 2021 and May 2022.
- Analysis of gene alterations from foundation testing (excluding variants of unknown significance).
- CGP samples were obtained from liver tumor biopsy, bone metastases surgical specimens, and blood.
Main Results:
- All nine patients had detectable gene alterations.
- The median number of prior systemic therapies was four.
- Seven patients were identified as candidates for clinical trials.
- One patient with high tumor mutation burden (TMB) became eligible for pembrolizumab treatment post-CGP.
Conclusions:
- CGP can reveal genomic alterations in uHCC patients after multiple molecular-targeted therapies.
- Further research is needed to develop personalized therapies and novel agents for HCC treatment based on these findings.
