ArticlePloS one2015
Dual fatty acid synthase and HER2 signaling blockade shows marked antitumor activity against breast cancer models resistant to anti-HER2 drugs.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- Targeting fatty acid metabolism for cancer therapy.Fundamental research · 2026Review
- Lipid Metabolic Reprogramming in Breast Cancer: Mechanisms and Emerging Therapeutic Strategies.Breast cancer (Dove Medical Press) · 2026Review
- Functional Role of Resveratrol in Inducing Apoptosis in Breast Cancer Subtypes via Inhibition of Intracellular Fatty Acid Synthase.Molecules (Basel, Switzerland) · 2025Article
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Involvement of microRNAs-449/FASN axis in response to trastuzumab therapy in HER2-positive breast cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- CD36 enrichment in HER2-positive mesenchymal stem cells drives therapy refractoriness in breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- HER2-Positive Breast Cancer Treatment and Resistance.Advances in experimental medicine and biology · 2025Review
- Rational Design of HER2-Targeted Combination Therapies to Reverse Drug Resistance in Fibroblast-Protected HER2+ Breast Cancer Cells.Cellular and molecular bioengineering · 2024Article
- Targeting fatty acid oxidation enhances response to HER2-targeted therapy.Nature communications · 2024Article
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- Rapidly Evolving Pre- and Post-surgical Systemic Treatment of Melanoma.American journal of clinical dermatology · 2024Review
- Targeting endogenous fatty acid synthesis stimulates the migration of ovarian cancer cells to adipocytes and promotes the transport of fatty acids from adipocytes to cancer cells.International journal of oncology · 2024Article
- Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation.Advances in experimental medicine and biology · 2024Review
- The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy.Frontiers in immunology · 2024Review
- Breast Cancer Chemoresistance: Insights into the Regulatory Role of lncRNA.International journal of molecular sciences · 2023Review
- Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma.Journal for immunotherapy of cancer · 2023Article
- Review
- Epigallocatechin gallate triggers apoptosis by suppressing de novo lipogenesis in colorectal carcinoma cells.FEBS open bio · 2022Article
- Association between fatty acid synthase and adipophilin expression in triple-negative breast cancer.Molecular and clinical oncology · 2022Article
- Gene signatures of circulating breast cancer cell models are a source of novel molecular determinants of metastasis and improve circulating tumor cell detection in patients.Journal of experimental & clinical cancer research : CR · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blocking the enzyme Fatty Acid Synthase (FASN) leads to apoptosis of HER2-positive breast carcinoma cells. The hypothesis is that blocking FASN, in combination with anti-HER2 signaling agents, would be an effective antitumor strategy in preclinical HER2+ breast cancer models of trastuzumab and lapatinib resistance. We developed and molecularly characterized in vitro HER2+ models of resistance to trastuzumab (SKTR), lapatinib (SKLR) and both (SKLTR). The cellular interactions of combining anti-FASN polyphenolic compounds (EGCG and the synthetic G28UCM) with anti-HER2 signaling drugs (trastuzumab plus pertuzumab and temsirolimus) were analyzed. Tumor growth inhibition after treatment with EGCG, pertuzumab, temsirolimus or the combination was evaluated in two in vivo orthoxenopatients: one derived from a HER2+ patient and another from a patient who relapsed on trastuzumab and lapatinib-based therapy. SKTR, SKLR and SKLTR showed hyperactivation of EGFR and p-ERK1/2 and PI3KCA mutations. Dual-resistant cells (SKLTR) also showed hyperactivation of HER4 and recovered levels of p-AKT compared with mono-resistant cells. mTOR, p-mTOR and FASN expression remained stable in SKTR, SKLR and SKLTR. In vitro, anti-FASN compounds plus pertuzumab showed synergistic interactions in lapatinib- and dual- resistant cells and improved the results of pertuzumab plus trastuzumab co-treatment. FASN inhibitors combined with temsirolimus displayed the strongest synergistic interactions in resistant cells. In vivo, both orthoxenopatients showed strong response to the antitumor activity of the combination of EGCG with pertuzumab or temsirolimus, without signs of toxicity. We showed that the simultaneous blockade of FASN and HER2 pathways is effective in cells and in breast cancer models refractory to anti-HER2 therapies.
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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.