Observational studyJournal of cellular physiology2019
Intratumor lactate levels reflect HER2 addiction status in HER2-positive breast cancer.
Observational study in Journal of cellular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Frontiers and hot topics in tumor metabolic reprogramming: a bibliometric analysis from 2014 to 2023.Frontiers in oncology · 2025Pooled it
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Breast Cancer Progression by the FGF/FGFR Axis: A Metabolic Perspective.Journal of mammary gland biology and neoplasia · 2025Review
- Lactate and lactylation in breast cancer: current understanding and therapeutic opportunities.Cancer biology & medicine · 2025Review
- Transmembrane Amino Acid Transporters in Shaping the Metabolic Profile of Breast Cancer Cell Lines: The Focus on Molecular Biological Subtype.Current issues in molecular biology · 2024Review
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance.Oncogene · 2024Review
- Review
- Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.Cancer cell · 2023Article
- Relationship Between Metabolic Activity, Cellularity, Histopathological Features of Primary Tumors and Distant Metastatic Potential in Breast Cancer.Molecular imaging and radionuclide therapy · 2023Article
- The Significance of Microenvironmental and Circulating Lactate in Breast Cancer.International journal of molecular sciences · 2023Review
- How Driver Oncogenes Shape and Are Shaped by Alternative Splicing Mechanisms in Tumors.Cancers · 2023Review
- Review
- Tumor Glucose and Fatty Acid Metabolism in the Context of Anthracycline and Taxane-Based (Neo)Adjuvant Chemotherapy in Breast Carcinomas.Frontiers in oncology · 2022Review
- Integrative Dissection of Novel Lactate Metabolism-Related Signature in the Tumor Immune Microenvironment and Prognostic Prediction in Breast Cancer.Frontiers in oncology · 2022Article
- Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.Cancer research · 2021Article
- Metabolic Flexibility Is a Determinant of Breast Cancer Heterogeneity and Progression.Cancers · 2021Review
- [Molecules (Basel, Switzerland) · 2021Article
- Hyperglycemia and Chemoresistance in Breast Cancer: From Cellular Mechanisms to Treatment Response.Frontiers in oncology · 2021Review
- Targeting Glucose Metabolism to Overcome Resistance to Anticancer Chemotherapy in Breast Cancer.Cancers · 2020Review
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
Despite different molecular tumor profiles indicate that human epidermal growth factor receptor 2 (HER2) messenger RNA (mRNA) levels mirror HER2 addiction and trastuzumab benefit in HER2-positive breast cancer (BC), the identification of noninvasive clinical predictors of trastuzumab sensitivity remains an unmet clinical need. In the current study, we investigated whether intratumor lactate levels reflect HER2 addiction and, in turn, trastuzumab susceptibility. Accordingly, the gene expression profiles of transgenic murine BC cell lines expressing the human d16HER2 variant (HER2-addicted) or human full-length HER2 (WTHER2; HER2-nonaddicted) revealed a significant enrichment of glycolysis-related gene pathways in HER2-addicted cells. We studied the metabolic content of 22 human HER2-positive BC by quantitative nuclear magnetic resonance spectroscopy and found that those cases with higher lactate levels were characterized by higher HER2 transcript levels. Moreover, gene expression analyses of HER2-positive BC samples from a TCGA data set revealed a significant enrichment in glycolysis-related pathways in high/HER2-addicted tumors. These data were confirmed by metabolic analyses of human HER2-positive BC cell lines with high or low HER2 transcript levels, which revealed significantly more active glycolytic metabolism in high HER2 transcript than in low HER2 transcript cells. Overall, our results provide evidence for noninvasive intratumor lactate detection as a potential metabolic biomarker of HER2 addiction and trastuzumab response suggesting the possibility to use in vivo imaging to assess lactate levels and, in turn, select HER2-positive BC patients who are more likely to benefit from anti-HER2 treatments.
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Registered trials
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