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Targeting IGF-IR improves neoadjuvant chemotherapy efficacy in breast cancers with low IGFBP7 expression

Godina, Christopher LU orcid ; Pollak, Michael N. and Jernström, Helena LU (2024) In NPJ precision oncology 8(1).
Abstract

There has been a long-standing interest in targeting the type 1 insulin-like growth factor receptor (IGF-1R) signaling system in breast cancer due to its key role in neoplastic proliferation and survival. However, no IGF-1R targeting agent has shown substantial clinical benefit in controlled phase 3 trials, and no biomarker has been shown to have clinical utility in the prediction of benefit from an IGF-1R targeting agent. IGFBP7 is an atypical insulin-like growth factor binding protein as it has a higher affinity for the IGF-1R than IGF ligands. We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab, an anti-IGF-1R monoclonal antibody, to neoadjuvant chemotherapy,... (More)

There has been a long-standing interest in targeting the type 1 insulin-like growth factor receptor (IGF-1R) signaling system in breast cancer due to its key role in neoplastic proliferation and survival. However, no IGF-1R targeting agent has shown substantial clinical benefit in controlled phase 3 trials, and no biomarker has been shown to have clinical utility in the prediction of benefit from an IGF-1R targeting agent. IGFBP7 is an atypical insulin-like growth factor binding protein as it has a higher affinity for the IGF-1R than IGF ligands. We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab, an anti-IGF-1R monoclonal antibody, to neoadjuvant chemotherapy, substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone. The pCR rate in the chemotherapy plus ganitumab arm was 46.9% in patients in the lowest quartile of IGFBP7 expression, in contrast to only 5.6% in the highest quartile. Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1R targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed.

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author
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type
Contribution to journal
publication status
published
subject
in
NPJ precision oncology
volume
8
issue
1
article number
212
publisher
Springer Nature
external identifiers
  • pmid:39362991
  • scopus:85205962546
ISSN
2397-768X
DOI
10.1038/s41698-024-00712-9
language
English
LU publication?
yes
id
8db7b2ef-1c5a-4d56-8c01-4046516f0962
date added to LUP
2024-11-27 10:53:13
date last changed
2025-01-22 15:55:23
@article{8db7b2ef-1c5a-4d56-8c01-4046516f0962,
  abstract     = {{<p>There has been a long-standing interest in targeting the type 1 insulin-like growth factor receptor (IGF-1R) signaling system in breast cancer due to its key role in neoplastic proliferation and survival. However, no IGF-1R targeting agent has shown substantial clinical benefit in controlled phase 3 trials, and no biomarker has been shown to have clinical utility in the prediction of benefit from an IGF-1R targeting agent. IGFBP7 is an atypical insulin-like growth factor binding protein as it has a higher affinity for the IGF-1R than IGF ligands. We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab, an anti-IGF-1R monoclonal antibody, to neoadjuvant chemotherapy, substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone. The pCR rate in the chemotherapy plus ganitumab arm was 46.9% in patients in the lowest quartile of IGFBP7 expression, in contrast to only 5.6% in the highest quartile. Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1R targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed.</p>}},
  author       = {{Godina, Christopher and Pollak, Michael N. and Jernström, Helena}},
  issn         = {{2397-768X}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{NPJ precision oncology}},
  title        = {{Targeting IGF-IR improves neoadjuvant chemotherapy efficacy in breast cancers with low IGFBP7 expression}},
  url          = {{http://dx.doi.org/10.1038/s41698-024-00712-9}},
  doi          = {{10.1038/s41698-024-00712-9}},
  volume       = {{8}},
  year         = {{2024}},
}