ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
IGFBP ratio confers resistance to IGF targeting and correlates with increased invasion and poor outcome in breast tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Immune and Growth Factor Signaling Pathways Are Associated with Pathologic Complete Response to an Anti-Type I Insulin-like Growth Factor Receptor Regimen in Patients with Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial.The Lancet. Oncology · 2014Trial
- Article
- Redundant Signaling as the Predominant Mechanism for Resistance to Antibodies Targeting the Type-I Insulin-Like Growth Factor Receptor in Cells Derived from Childhood Sarcoma.Molecular cancer therapeutics · 2023Article
- Decoding Insulin-Like Growth Factor Signaling Pathway From a Non-coding RNAs Perspective: A Step Towards Precision Oncology in Breast Cancer.Journal of mammary gland biology and neoplasia · 2022Review
- Biological effects and regulation of IGFBP5 in breast cancer.Frontiers in endocrinology · 2022Review
- Protein‑ and growth‑modulatory effects of carcinoma‑associated fibroblasts on breast cancer cells: Role of interleukin‑6.International journal of oncology · 2020Article
- The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis.Scientific reports · 2016Article
- Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer.BMC cancer · 2016Article
- An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression.Human molecular genetics · 2016Article
- IGFBP-2 and -5: important regulators of normal and neoplastic mammary gland physiology.Journal of cell communication and signaling · 2015Article
- Clinical significance of miR-140-5p and miR-193b expression in patients with breast cancer and relationship to IGFBP5.Genetics and molecular biology · 2015Article
- The role of the insulin-like growth factor-1 system in breast cancer.Molecular cancer · 2015Review
- Insulin-like growth factor--phosphatidylinositol 3 kinase signaling in canine cortisol-secreting adrenocortical tumors.Journal of veterinary internal medicine · 2015Article
- The Role of the Insulin/IGF System in Cancer: Lessons Learned from Clinical Trials and the Energy Balance-Cancer Link.Frontiers in endocrinology · 2015Review
- Understanding the Key to Targeting the IGF Axis in Cancer: A Biomarker Assessment.Frontiers in oncology · 2015Review
- Insulin-like growth factor and epidermal growth factor signaling in breast cancer cell growth: focus on endocrine resistant disease.Analytical cellular pathology (Amsterdam) · 2015Review
- Estrogen Receptor-β and the Insulin-Like Growth Factor Axis as Potential Therapeutic Targets for Triple-Negative Breast Cancer.Critical reviews in oncogenesis · 2015Review
- Can we unlock the potential of IGF-1R inhibition in cancer therapy?Cancer treatment reviews · 2014Review
- Symbolic data analysis to defy low signal-to-noise ratio in microarray data for breast cancer prognosis.Journal of computational biology : a journal of computational molecular cell biology · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo improve the significance of insulin-like growth factor-binding protein 5 (IGFBP-5) as a prognostic and potentially predictive marker in patients with breast cancer. EXPERIMENTAL
designIncreased IGFBP-5 expression was identified in MCF-7 cells resistant (MCF-7R4) to the IGF-1R/insulin receptor (InsR) inhibitor BMS-536924 and its role examined by targeted knockdown and overexpression in multiple experimental models. Protein expression of IGFBP-5 was measured by immunohistochemistry in a cohort of 76 patients with breast cancer to examine correlative associations with invasive tumor fraction and outcome. The use of a combined IGFBP-5/IGFBP-4 (BPR) expression ratio was applied to predict anti-IGF-1R/InsR response in a panel of breast cancer lines and outcome in multiple breast tumor cohorts.
resultsIGFBP-5 knockdown decreased BMS-536924 resistance in MCF-7R4 cells, whereas IGFBP-5 overexpression in MCF-7 cells conferred resistance. When compared with pathologically normal reduction mammoplasty tissue, IGFBP-5 expression levels were upregulated in both invasive and histologically normal adjacent breast cancer tissue. In both univariate and multivariate modeling, metastasis-free survival, recurrence free survival (RFS), and overall survival (OS) were significantly associated with high IGFBP-5 expression. Prognostic power of IGFBP-5 was further increased with the addition of IGFBP-4 where tumors were ranked based upon IGFBP-5/IGFBP-4 expression ratio (BPR). Multiple breast cancer cohorts confirm that BPR (high vs. low) was a strong predictor of RFS and OS.
conclusionIGFBP-5 expression is a marker of poor outcome in patients with breast cancer. An IGFBP-5/IGFBP-4 expression ratio may serve as a surrogate biomarker of IGF pathway activation and predict sensitivity to anti-IGF-1R targeting.
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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.