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Pharmaceuticals
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Insulin-Like Growth Factor-1 (IGF-1) Receptor as Drug Targets
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Insulin-Like Growth Factor-1 (IGF-1) Receptor as Drug Targets

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 5803

Special Issue Editors

Dr. Kornelia Kuźnik-Trocha

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Guest Editor
Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland
Interests: connective tissue diseases; pathology of the extracellular matrix; growth factors; systemic sclerosis; juvenile idiopathic arthritis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Katarzyna Winsz-Szczotka

E-Mail Website
Guest Editor
Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Sosnowiec, Poland
Interests: connective tissue diseases; pathology of the extracellular matrix; growth factors; juvenile idiopathic arthritis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Insulin-like growth factor 1 (IGF-1) plays an important role in human development, growth, and aging. IGF-1 exerts its effects through specific receptors located on cell membranes, i.e., IGF-R (insulin-like growth factor-1 and 2 receptors). Through these receptors, IGF-1 induces cell growth, affects cell survival by preventing apoptosis, and stimulates cell differentiation. Abnormal IGF signaling may lead to changes in systemic homeostasis, including cognitive dysfunction, development of neurodegenerative diseases, and most importantly, malignant transformation and tumor progression. In tumorigenesis, IGF-1 and its receptor are constitutively overexpressed. Increasing evidence suggests that the IGF axis not only promotes oncogenesis but also confers resistance to standard treatment. Given the high mortality rate of cancer patients, novel therapeutic targets are urgently needed. Hence, regulation of IGF-1/IGF-1R axis signaling appears to be a promising strategy leading to the disruption of cancer cell growth and survival.

In this Special Issue, we aim to draw together research results from experts in the field, thus providing the rationale for targeting IGF axis in cancer-therapeutic strategies, and to identify future directions of therapies.

Dr. Kornelia Kuźnik-Trocha
Prof. Dr. Katarzyna Winsz-Szczotka
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • insulin-like growth factor
  • insulin-like growth factor receptor
  • IGF-1/IGF-1R axis signaling
  • IGF-1/IGF-1R axis as a therapeutic target
  • IGF-1/IGF-1R-dependent diseases

Published Papers (3 papers)

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Research

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21 pages, 17509 KiB  
Article
Comparison of Bevacizumab and Aflibercept for Suppression of Angiogenesis in Human Retinal Microvascular Endothelial Cells
by Amirfarbod Yazdanyar, Charles L. Cai, Jacob V. Aranda, Eric Shrier and Kay D. Beharry
Pharmaceuticals 2023, 16(7), 939; https://doi.org/10.3390/ph16070939 - 29 Jun 2023
Viewed by 1358
Abstract
Bevacizumab (Avastin) is a vascular endothelial growth factor (VEGF) inhibitor that is widely used for aggressive posterior retinopathy of prematurity (APROP). Its use is associated with multiple adverse effects. Aflibercept (Eylea) is a VEGFR-1 analogue that is approved for ocular use, but its [...] Read more.
Bevacizumab (Avastin) is a vascular endothelial growth factor (VEGF) inhibitor that is widely used for aggressive posterior retinopathy of prematurity (APROP). Its use is associated with multiple adverse effects. Aflibercept (Eylea) is a VEGFR-1 analogue that is approved for ocular use, but its efficacy for APROP is less studied. We tested the hypothesis that Eylea is as effective as Avastin for suppression of intermittent hypoxia (IH)-induced angiogenesis. Human retinal microvascular endothelial cells (HRECs) were treated with Avastin and low- or high-dose Eylea and exposed to normoxia, hyperoxia (50% O2), or neonatal IH for 24, 48, or 72 h. Cells were assessed for migration and tube formation capacities, as well as biomarkers of angiogenesis and oxidative stress. Both doses of Eylea suppressed migration and tube formation in all oxygen environments, although the effect was not as robust as Avastin. Furthermore, the lower dose of Eylea appeared to be more effective than the higher dose. Eylea induced soluble VEGFR-1 (sVEGFR-1) coincident with high IGF-I levels and decreased Notch/Jagged-1, demonstrating a functional association. Given the role of VEGFR-1 and Notch as guidance cues for vascular sprouting, these data suggest that Eylea may promote normal vascular patterning in a dose-dependent manner. Full article
(This article belongs to the Special Issue Insulin-Like Growth Factor-1 (IGF-1) Receptor as Drug Targets)
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14 pages, 2256 KiB  
Article
Targeting the IGF-Axis in Cultured Pediatric High-Grade Glioma Cells Inhibits Cell Cycle Progression and Survival
by Yinhsuan Michely Chen, Matthew Leibovitch, Michele Zeinieh, Nada Jabado and Pnina Brodt
Pharmaceuticals 2023, 16(2), 297; https://doi.org/10.3390/ph16020297 - 14 Feb 2023
Cited by 1 | Viewed by 1383
Abstract
Pediatric high-grade gliomas (pHGG) accounts for approximately 8–12% of primary brain tumors in children. Prognosis is poor, with a median survival of 9–15 months. Insulin-like growth factor 1-receptor (IGF-1R) gene amplifications have been identified in high-grade gliomas and may contribute to its highly [...] Read more.
Pediatric high-grade gliomas (pHGG) accounts for approximately 8–12% of primary brain tumors in children. Prognosis is poor, with a median survival of 9–15 months. Insulin-like growth factor 1-receptor (IGF-1R) gene amplifications have been identified in high-grade gliomas and may contribute to its highly aggressive phenotype, but the effect of IGF inhibitors on pHGG is yet to be determined. In the present study, we analyzed the response of patient-derived pediatric high-grade glioma cells to a novel IGF-1R inhibitor, the IGF-Trap. Using immunohistochemistry, we found that IGF-1R was localized to both the nucleus and cell membrane in different pHGG patient-derived xenograft (PDX) lines under basal conditions. In response to ligand binding, nuclear levels of the receptor increased, and this was associated with the transcriptional upregulation of both the receptor and cyclin D1, suggesting that IGF-1R could regulate its own expression and cell cycle progression in these cells. Insulin-like growth factor-1 (IGF-1) increased the proliferation of the pHGG cells DIPG13 and SGJ2, and this could be blocked by the addition of the IGF-Trap. The IGF-Trap reduced the colony formation of these cells in an optimal growth medium and impeded the ability of IGF-1 to rescue DIPG13 cells from starvation-induced apoptosis. Collectively, these results implicate the IGF-1 axis in the regulation of cell cycle progression, cellular proliferation, and cell survival in pHGG, and identify the IGF-axis as a target and the IGF-Trap as a potential inhibitor of this axis in pHGG. Full article
(This article belongs to the Special Issue Insulin-Like Growth Factor-1 (IGF-1) Receptor as Drug Targets)
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Review

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10 pages, 511 KiB  
Review
Insulin-like Growth Factor-1 (IGF-1) Related Drugs in Pain Management
by Seokhyun Jin and Jianguo Cheng
Pharmaceuticals 2023, 16(5), 760; https://doi.org/10.3390/ph16050760 - 18 May 2023
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Abstract
Objective. The aim of this review is to explore the role of IGF-1 and IGF-1R inhibitors in pain-related conditions and assess the effectiveness of IGF-1-related drugs in pain management. Specifically, this paper investigates the potential involvement of IGF-1 in nociception, nerve regeneration, [...] Read more.
Objective. The aim of this review is to explore the role of IGF-1 and IGF-1R inhibitors in pain-related conditions and assess the effectiveness of IGF-1-related drugs in pain management. Specifically, this paper investigates the potential involvement of IGF-1 in nociception, nerve regeneration, and the development of neuropathic pain. Methods. We conducted a search of the PUBMED/MEDLINE database, Scopus, and the Cochrane Library for all reports published in English on IGF-1 in pain management from origination through November 2022. The resulting 545 articles were screened, and 18 articles were found to be relevant after reading abstracts. After further examination of the full text of these articles, ten were included in the analysis and discussion. The levels of clinical evidence and implications for recommendations of all the included human studies were graded. Results. The search yielded 545 articles, of which 316 articles were deemed irrelevant by reading the titles. There were 18 articles deemed relevant after reading abstracts, of which 8 of the reports were excluded due to lack of IGF-1-related drug treatment after reviewing the full text of the articles. All ten articles were retrieved for analysis and discussion. We found that IGF-1 may have several positive effects on pain management, including promoting the resolution of hyperalgesia, preventing chemotherapy-induced neuropathy, reversing neuronal hyperactivity, and elevating the nociceptive threshold. On the other hand, IGF-1R inhibitors may alleviate pain in mice with injury of the sciatic nerve, bone cancer pain, and endometriosis-induced hyperalgesia. While one study showed marked improvement in thyroid-associated ophthalmopathy in humans treated with IGF-1R inhibitor, two other studies did not find any benefits from IGF-1 treatment. Conclusions. This review highlights the potential of IGF-1 and IGF-1R inhibitors in pain management, but further research is needed to fully understand their efficacy and potential side effects. Full article
(This article belongs to the Special Issue Insulin-Like Growth Factor-1 (IGF-1) Receptor as Drug Targets)
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