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Aiming for the Insulin-like Growth Factor-1 system in breast cancer therapeutics
Panagiotis F Christopoulos1, Alexandre Corthay2, Michael Koutsilieris3
1Department of Experimental Physiology, Medical School, National & Kapodistrian University of Athens, Athens, Greece; Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University Hospital and University of Oslo, Oslo, Norway; Department of Medical Biology, Faculty of Health Sciences, UiT the Arctic University of Norway, Tromsø, Norway.
Abstract:
Despite the major discoveries occurred in oncology the recent years, breast malignancies remain one of the most common causes of cancer-related deaths for women in developed countries. Development of HER2-targeting drugs has been considered a breakthrough in anti-cancer approaches and alluded to the potential of targeting growth factors in breast cancer (BrCa) therapeutics. More than twenty-five years have passed since the Insulin-like Growth Factor-1 (IGF-1) system was initially recognized as a potential target candidate in BrCa therapy. To date, a growing body of studies have implicated the IGF-1 signaling with the BrCa biology. Despite the promising experimental evidence, the impression from clinical trials is rather disappointing. Several reasons may account for this and the last word regarding the efficacy of this system as a target candidate in BrCa therapeutics is probably not written yet. Herein, we provide the theoretical basis, as well as, a comprehensive overview of the current literature, regarding the different strategies targeting the various components of the IGF-1/IGF-1R axis in several pathophysiological aspects of BrCa, including the tumor micro-environment and cancer stemness. In addition, we review the rationale for targeting the IGF-1 system in the different BrCa molecular subtypes and in treatment resistant breast tumors with a focus on both the molecular mechanisms and on the clinical perspectives of such approaches in specific population subgroups. We also discuss the future challenges, as well as, the development of novel molecules and strategies targeting the system and suggest potential improvements in the field.
Insights
Targeting the Insulin-like Growth Factor-1 (IGF-1) system shows promise for breast cancer (BrCa) therapy, despite disappointing clinical trial results. Further research into IGF-1/IGF-1R axis strategies may improve treatment for various BrCa subtypes and resistant tumors.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Breast cancer remains a leading cause of cancer death in women, highlighting the need for novel therapeutic targets.
- The Insulin-like Growth Factor-1 (IGF-1) system has been recognized for over 25 years as a potential target in breast cancer (BrCa) therapy.
- While HER2-targeting drugs represent a breakthrough, the IGF-1 system's clinical efficacy in BrCa remains under investigation despite extensive research.
Purpose of the Study:
- To provide a comprehensive overview of targeting the IGF-1/IGF-1R axis in breast cancer.
- To explore strategies for targeting the IGF-1 system in various pathophysiological aspects of BrCa, including tumor micro-environment and cancer stemness.
- To review the rationale and clinical perspectives of targeting the IGF-1 system in different BrCa molecular subtypes and treatment-resistant tumors.
Main Methods:
- Comprehensive literature review of studies on the IGF-1/IGF-1R axis in breast cancer.
- Analysis of theoretical basis and current literature regarding different targeting strategies.
- Focus on molecular mechanisms, clinical perspectives, and specific population subgroups.
Main Results:
- The IGF-1 signaling pathway is implicated in various aspects of BrCa biology, including tumor micro-environment and cancer stemness.
- Experimental evidence suggests potential for targeting the IGF-1 system, but clinical trial outcomes have been disappointing.
- Specific strategies are being investigated for different BrCa molecular subtypes and treatment-resistant tumors.
Conclusions:
- Despite past clinical disappointments, the IGF-1/IGF-1R axis remains a relevant target for breast cancer therapy.
- Novel molecules and strategies are being developed to overcome challenges and improve targeting efficacy.
- Further research and improved approaches are needed to fully realize the therapeutic potential of the IGF-1 system in BrCa.
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