ArticleOncogene2021
Mutations in circulating tumor DNA predict primary resistance to systemic therapies in advanced hepatocellular carcinoma.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 126 citations in OpenAlex.
- Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase II clinical trial.Journal for immunotherapy of cancer · 2022Trial
- Prediction of Response to Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?Cancers · 2026Review
- Clinical Feasibility of Circulating Tumor DNA in Patients with Advanced Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab.Liver cancer · 2026Article
- Review
- Artificial intelligence-powered liquid biopsy in cancer: a paradigm shift in cancer detection and personalized care.Cancer cell international · 2026Review
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- Screening, Prognostic, and Predictive Molecular Tools for Colorectal Cancer: Recent Advances in the Classical Background.International journal of molecular sciences · 2026Review
- Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signaling.Nature genetics · 2026Article
- A Phase 1b Study of Lenvatinib plus Nivolumab in Patients with Unresectable Hepatocellular Carcinoma.Liver cancer · 2026Article
- Tumor-based biomarkers and circulating tumor DNA for precision medicine in advanced hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- Advancing precision medicine in hepatocellular carcinoma: current challenges and future directions in liquid biopsy, immune microenvironment, single nucleotide polymorphisms, and conversion therapy.Hepatic oncology · 2025Review
- Expression landscape of epigenetic genes in human hepatocellular carcinoma.Journal of physiology and biochemistry · 2025Article
- Article
- Liquid Biopsy in Hepatocellular Carcinoma: ctDNA as a Potential Biomarker for Diagnosis and Prognosis.Current oncology reports · 2025Review
- The Current Role of Circulating Cell-Free DNA in the Management of Hepatocellular Carcinoma.Cancers · 2025Review
- An Artificial Intelligence Pipeline for Hepatocellular Carcinoma: From Data to Treatment Recommendations.International journal of general medicine · 2025Review
- Correlation analysis between plasma circulating tumour deoxyribonucleic acid variations and survival in patients with hepatocellular carcinoma.Frontiers in oncology · 2025Article
- Development of a genetically tailored implantation hepatocellular carcinoma model in Oncopigs by somatic cell CRISPR editing.Disease models & mechanisms · 2025Article
- Assessing the Causal Effect of Circulating Protein-To-Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma.Cancer medicine · 2025Article
- Novel biomarkers for monitoring and management of hepatocellular carcinoma.Cancer cell international · 2024Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Little is known about the mutational landscape of advanced hepatocellular carcinoma (HCC), and predictive biomarkers of response to systemic therapies are lacking. We aimed to describe the mutational landscape of advanced HCC and to identify predictors of primary resistance to systemic therapies using circulating tumor DNA (ctDNA). We prospectively enrolled 121 patients between October 2015 and January 2019. We performed targeted ultra-deep sequencing of 25 genes and Digital Droplet PCR of TERT promoter, including sequential samples throughout treatment. Primary endpoint was progression-free survival (PFS) stratified by mutation profiles in ctDNA. Secondary endpoints were overall survival and objective response rate. The most frequent mutations in ctDNA of advanced HCC were TERT promoter (51%), TP53 (32%), CTNNB1 (17%), PTEN (8%), AXIN1, ARID2, KMT2D, and TSC2 (each 6%). TP53 and CTNNB1 mutations were mutually exclusive. Patients with mutations in the PI3K/MTOR pathway had significantly shorter PFS than those without these mutations after tyrosine kinase inhibitors (2.1 vs 3.7 months, p < 0.001), but not after immune checkpoint inhibition (CPI). WNT pathway mutations were not associated with PFS, overall survival, or objective response after CPI. Serial profiling of ctDNA in a subset correlated with treatment response. Mutation profiling of ctDNA in advanced HCC shows similar mutation frequencies for known HCC drivers compared to early stages and identifies predictive biomarkers of response to systemic therapies.
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