Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Soni, Upendra K., Jenny, Liam, Hegde, Rashmi S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
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
_version_ 1785123541896658944
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
work_keys_str_mv AT soniupendrak igf1rtargetingincancerdoessubcellularlocalizationmatter
AT jennyliam igf1rtargetingincancerdoessubcellularlocalizationmatter
AT hegderashmis igf1rtargetingincancerdoessubcellularlocalizationmatter