A1 Refereed original research article in a scientific journal
Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer
Authors: Ireland L, Santos A, Campbell F, Figueiredo C, Hammond D, Ellies LG, Weyer-Czernilofsky U, Bogenrieder T, Schmid M, Mielgo A
Publication year: 2018
Journal: Oncogene
Journal name in source: Oncogene
Journal acronym: Oncogene
Volume: 37
Issue: 15
First page : 2022
Last page: 2036
Number of pages: 15
ISSN: 0950-9232
eISSN: 1476-5594
DOI: https://doi.org/10.1038/s41388-017-0115-x
Web address : https://www.nature.com/articles/s41388-017-0115-x.pdf
Self-archived copy’s web address: https://www.nature.com/articles/s41388-017-0115-x.pdf
Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation.
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