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IGF-1R targeting in cancer – does sub-cellular localization matter?
The insulin-like growth factor receptor (IGF-1R) was among the most intensively pursued kinase targets in oncology. However, even after a slew of small-molecule and antibody therapeutics reached clinical trials for a range of solid tumors, the initial promise remains unfulfilled. Mechanisms of resis...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588251/ https://www.ncbi.nlm.nih.gov/pubmed/37858153 http://dx.doi.org/10.1186/s13046-023-02850-7 |
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author | Soni, Upendra K. Jenny, Liam Hegde, Rashmi S. |
author_facet | Soni, Upendra K. Jenny, Liam Hegde, Rashmi S. |
author_sort | Soni, Upendra K. |
collection | PubMed |
description | The insulin-like growth factor receptor (IGF-1R) was among the most intensively pursued kinase targets in oncology. However, even after a slew of small-molecule and antibody therapeutics reached clinical trials for a range of solid tumors, the initial promise remains unfulfilled. Mechanisms of resistance to, and toxicities resulting from, IGF-1R-targeted drugs are well-catalogued, and there is general appreciation of the fact that a lack of biomarker-based patient stratification was a limitation of previous clinical trials. But no next-generation therapeutic strategies have yet successfully exploited this understanding in the clinic. Currently there is emerging interest in re-visiting IGF-1R targeted therapeutics in combination-treatment protocols with predictive biomarker-driven patient-stratification. One such biomarker that emerged from early clinical trials is the sub-cellular localization of IGF-1R. After providing some background on IGF-1R, its drugging history, and the trials that led to the termination of drug development for this target, we look more deeply into the correlation between sub-cellular localization of IGF-1R and susceptibility to various classes of IGF-1R - targeted agents. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02850-7. |
format | Online Article Text |
id | pubmed-10588251 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105882512023-10-21 IGF-1R targeting in cancer – does sub-cellular localization matter? Soni, Upendra K. Jenny, Liam Hegde, Rashmi S. J Exp Clin Cancer Res Review The insulin-like growth factor receptor (IGF-1R) was among the most intensively pursued kinase targets in oncology. However, even after a slew of small-molecule and antibody therapeutics reached clinical trials for a range of solid tumors, the initial promise remains unfulfilled. Mechanisms of resistance to, and toxicities resulting from, IGF-1R-targeted drugs are well-catalogued, and there is general appreciation of the fact that a lack of biomarker-based patient stratification was a limitation of previous clinical trials. But no next-generation therapeutic strategies have yet successfully exploited this understanding in the clinic. Currently there is emerging interest in re-visiting IGF-1R targeted therapeutics in combination-treatment protocols with predictive biomarker-driven patient-stratification. One such biomarker that emerged from early clinical trials is the sub-cellular localization of IGF-1R. After providing some background on IGF-1R, its drugging history, and the trials that led to the termination of drug development for this target, we look more deeply into the correlation between sub-cellular localization of IGF-1R and susceptibility to various classes of IGF-1R - targeted agents. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-023-02850-7. BioMed Central 2023-10-20 /pmc/articles/PMC10588251/ /pubmed/37858153 http://dx.doi.org/10.1186/s13046-023-02850-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Soni, Upendra K. Jenny, Liam Hegde, Rashmi S. IGF-1R targeting in cancer – does sub-cellular localization matter? |
title | IGF-1R targeting in cancer – does sub-cellular localization matter? |
title_full | IGF-1R targeting in cancer – does sub-cellular localization matter? |
title_fullStr | IGF-1R targeting in cancer – does sub-cellular localization matter? |
title_full_unstemmed | IGF-1R targeting in cancer – does sub-cellular localization matter? |
title_short | IGF-1R targeting in cancer – does sub-cellular localization matter? |
title_sort | igf-1r targeting in cancer – does sub-cellular localization matter? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10588251/ https://www.ncbi.nlm.nih.gov/pubmed/37858153 http://dx.doi.org/10.1186/s13046-023-02850-7 |
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