ArticleOncotarget2014
Identification of novel therapeutic targets in the PI3K/AKT/mTOR pathway in hepatocellular carcinoma using targeted next generation sequencing.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 94 citations in OpenAlex.
- Protein lactylation in metabolic dysfunction-associated steatotic liver disease: a mechanistic review.Diabetology & metabolic syndrome · 2026Review
- Driver mutation impact in Chinese hepatocellular carcinoma.PloS one · 2026Article
- Impact of alcohol-associated and metabolic dysfunction-associated steatotic liver diseases upon hepatic disorder and carcinogenesis in the current era.World journal of hepatology · 2025Article
- LincRNA-miR interactions in hepatocellular carcinoma: comprehensive review and in silico analysis: a step toward ncRNA precision.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Hepatocellular carcinoma in patients without cirrhosis.World journal of gastroenterology · 2025Review
- Deciphering gene expression patterns using large-scale transcriptomic data and its applications.Briefings in bioinformatics · 2024Article
- Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Connecting the mechanisms of tumor sex differences with cancer therapy.Molecular and cellular biochemistry · 2024Review
- Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2023Review
- Tanshinone IIA and hepatocellular carcinoma: A potential therapeutic drug.Frontiers in oncology · 2023Review
- The Role of CTNNA1 in Malignancies: An Updated Review.Journal of Cancer · 2023Review
- Non-alcoholic fatty liver disease and hepatocellular carcinoma: Clinical challenges of an intriguing link.World journal of gastroenterology · 2022Review
- Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach.Cancers · 2021Review
- Review
- Article
- [Antitumor effects of AZD2014, a dual mTORC1/2 inhibitor, against human hepatocellular carcinoma xenograft in nude mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- TSC1/2 mutations-a unique type of mutation suitable for liver transplantation of Hepatocellular carcinoma.Journal of gastrointestinal oncology · 2021Article
- Hepatocrinology.Medical sciences (Basel, Switzerland) · 2021Review
- Current status of ctDNA in precision oncology for hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Understanding genetic aberrations in cancer leads to discovery of new targets for cancer therapies. The genomic landscape of hepatocellular carcinoma (HCC) has not been fully described. Therefore, patients with refractory advanced/metastatic HCC referred for experimental therapies, who had adequate tumor tissue available, had targeted next generation sequencing (NGS) of their tumor samples using the Illumina HiSeq 2000 platform (Foundation One, Foundation Medicine, MA) and their treatment outcomes were analyzed. In total, NGS was obtained for 14 patients (median number of prior therapies, 1) with advanced/metastatic HCC. Of these 14 patients, 10 (71%) were men, 4 (29%) women, 6 (43%) had hepatitis B or C-related HCC. NGS revealed at least 1 molecular abnormality in 12 patients (range 0-8, median 2). Detected molecular aberrations led to putative activation of the PI3K/AKT/mTOR pathway (n=3 [mTOR, PIK3CA, NF1]), Wnt pathway (n=6 [CTNNA1, CTNNB1]), MAPK pathway (n=2 [MAP2K1, NRAS]), and aberrant DNA repair mechanisms, cell cycle control and apoptosis (n=18 [ATM, ATR, BAP1, CCND1, CDKN2A, CDK4, FGF3, FGF4, FGF19, MCL1, MDM2, RB1, TP53]). Of the 3 patients with molecular aberrations putatively activating the PI3K/AKT/mTOR pathway, 2 received therapies including a mTOR inhibitor and all demonstrated therapeutic benefit ranging from a partial response to minor shrinkage per RECIST (-30%, -15%; respectively). In conclusion, genomic alterations are common in advanced HCC. Refractory patients with alterations putatively activating the PI3K/AKT/mTOR pathway demonstrated early signals of clinical activity when treated with therapies targeting mTOR.
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