ArticleInternational journal of cancer2020
IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer.
Article in International journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- CAFs and Endocrine Therapy Resistance in Hormone Receptor-Positive Breast Cancer.International journal of molecular sciences · 2026Review
- MAPK signaling mediates tamoxifen resistance in estrogen receptor-positive breast cancer.Molecular and cellular biochemistry · 2025Review
- Adipocyte/Tumor cell crosstalk via IGF-1/TXNIP axis promotes malignancy and endocrine resistance in breast cancer.Cell communication and signaling : CCS · 2025Article
- Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.Neuro-oncology · 2024Article
- Insulin receptor alternative splicing in breast and prostate cancer.Cancer cell international · 2024Review
- Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.MedComm · 2023Review
- Pan-cancer analysis of oncogenic role of insulin-like growth factor-binding proteins and validation in ovarian cancer.Cancer medicine · 2023Article
- A scoping review of statistical methods in studies of biomarker-related treatment heterogeneity for breast cancer.BMC medical research methodology · 2023Article
- Article
- Obesity and endocrine-related cancer: The important role of IGF-1.Frontiers in endocrinology · 2023Review
- Review
- Identification of potential target genes of honokiol in overcoming breast cancer resistance to tamoxifen.Frontiers in oncology · 2022Article
- Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer: a prospective cohort study.Carcinogenesis · 2021Article
- Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection.Biomedicines · 2021Review
- Diversity of insulin and IGF signaling in breast cancer: Implications for therapy.Molecular and cellular endocrinology · 2021Review
- Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers.Frontiers in cell and developmental biology · 2021Review
- The Interplay Between Non-coding RNAs and Insulin-Like Growth Factor Signaling in the Pathogenesis of Neoplasia.Frontiers in cell and developmental biology · 2021Review
- Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2020Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib.
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