ArticleCellular oncology (Dordrecht, Netherlands)2023
Fatty acid synthase as a new therapeutic target for HER2-positive gastric cancer.
Article in Cellular oncology (Dordrecht, Netherlands), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 20 citations in OpenAlex.
- Molecular classification and precision therapy in gastric cancer: Current advances and future perspectives (Review).Oncology reports · 2026Review
- The novel oleanolic acid derivative ZQL-4c modulates trastuzumab resistance in HER2+ breast cancer by inhibiting SCD-mediated lipid metabolism disorders.Cancer cell international · 2026Article
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects.Genes & diseases · 2026Review
- Targeting fatty acid synthase suppresses tumor development in NF2/CDKN2A-deficient pleural mesothelioma.Cell death & disease · 2026Article
- Lipid Metabolic Reprogramming in Breast Cancer: Mechanisms and Emerging Therapeutic Strategies.Breast cancer (Dove Medical Press) · 2026Review
- Discovery of highly potent marine-derived compound Penicolinate H reveals SREBP-1 mediated lipogenesis as a druggable vulnerability in gastric cancer.Journal of translational medicine · 2025Article
- Recent advances in understanding the relationship between lipid metabolism and immune escape in the tumor microenvironment of gastric cancer.Medical review (2021) · 2025Review
- Lipid metabolism-related genes in gastric cancer: Exploring oncogenic pathways.World journal of gastrointestinal oncology · 2025Review
- The EGR1-mediated lncRNA TENM3-AS1 potentiates gastric cancer metastasis via reprogramming fatty acid metabolism.Molecular cancer · 2025Article
- Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma.Journal of translational medicine · 2025Article
- CD36 enrichment in HER2-positive mesenchymal stem cells drives therapy refractoriness in breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Elucidating the Role of FASN in Lung Cancer Stem Cells in Sensitive and Resistant EGFR-Mutated Non-Small Cell Lung Cancer Cells.Lung Cancer (Auckland, N.Z.) · 2025Article
- HER2-positive gastric cancer: from targeted therapy to CAR-T cell therapy.Frontiers in immunology · 2025Review
- Theranostic Approaches for Gastric Cancer: An Overview of In Vitro and In Vivo Investigations.Cancers · 2024Review
- Membrane RRM2-positive cells represent a malignant population with cancer stem cell features in intrahepatic cholangiocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.Frontiers in pharmacology · 2024Review
- Reprogrammed lipid metabolism in advanced resistant cancers: an upcoming therapeutic opportunity.Cancer drug resistance (Alhambra, Calif.) · 2024Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
purposeTrastuzumab is an HER2-specific agent approved as the gold-standard therapy for advanced HER2-positive (HER2+) gastric cancer (GC), but the high rate and rapid appearance of resistance limit its clinical efficacy, resulting in the need to identify new vulnerabilities. Defining the drivers influencing HER2+ cancer stem cell (CSC) maintenance/survival could represent a clinically useful strategy to counteract tumor growth and therapy resistance. Accumulating evidence show that targeting crucial metabolic hubs, as the fatty acid synthase (FASN), may be clinically relevant.
methodsFASN protein and transcript expression were examined by WB and FACS and by qRT-PCR and GEP analyses, respectively, in trastuzumab-sensitive and trastuzumab-resistant HER2+ GC cell lines cultured in adherent (2D) or gastrosphere promoting (3D) conditions. Molecular data were analyzed in silico in public HER2+ GC datasets. The effectiveness of the FASN inhibitor TVB3166 to overcome anti-HER2 therapy resistance was tested in vitro in gastrospheres forming efficiency bioassays and in vivo in mice bearing trastuzumab-resistant GC cells.
resultsWe compared the transcriptome profiles of HER2+ GC cells cultured in 2D versus 3D conditions finding a significant enrichment of FASN in 3D cultures. FASN upregulation significantly correlated with high stemness score and poor prognosis in HER2+ GC cases. TVB3166 treatment significantly decreased GCSCs in all cell targets. HER2 and FASN cotargeting significantly decreased the capability to form gastrospheres versus monotherapy and reduced the in vivo growth of trastuzumab-resistant GC cells.
conclusionOur findings indicate that cotargeting HER2 and FASN increase the benefit of anti-HER2 therapy representing a new opportunity for metabolically combating trastuzumab-resistant HER2+ GC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.