ArticleOncotarget2017
Enhanced response of melanoma cells to MEK inhibitors following unbiased IGF-1R down-regulation.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Review
- IGF-1R is a molecular determinant for response to p53 reactivation therapy in conjunctival melanoma.Oncogene · 2022Article
- Skin anomalies in acromegalic patients (Review of the practical aspects).Experimental and therapeutic medicine · 2021Review
- Aldehyde dehydrogenase-positive melanoma stem cells in tumorigenesis, drug resistance and anti-neoplastic immunotherapy.Molecular biology reports · 2020Review
- Insulin Reduces the Efficacy of Vemurafenib and Trametinib in Melanoma Cells.Cancer management and research · 2020Article
- Review
- Platelet-Derived Growth Factor Receptor and Ionizing Radiation in High Grade Glioma Cell Lines.International journal of molecular sciences · 2019Article
- Arrestin-β-1 Physically Scaffolds TSH and IGF1 Receptors to Enable Crosstalk.Endocrinology · 2019Article
- A multitargeted probe-based strategy to identify signaling vulnerabilities in cancers.The Journal of biological chemistry · 2019Article
- Insulin-like Growth Factor-I Receptor and Thyroid-Associated Ophthalmopathy.Endocrine reviews · 2019Review
- Personalized Medicine in Malignant Melanoma: Towards Patient Tailored Treatment.Frontiers in oncology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to its ability to compensate for signals lost following therapeutic MAPK-inhibition, insulin-like growth factor type 1 receptor (IGF-1R) co-targeting is a rational approach for melanoma treatment. However IGF-1R conformational changes associated with its inhibition can preferentially activate MAPK-pathway in a kinase-independent manner, through a process known as biased signaling. We explored the impact of biased IGF-1R signaling, on response to MAPK inhibition in a panel of skin melanoma cell lines with differing MAPK and p53 mutation statuses. Specific siRNA towards IGF-1R down-regulates the receptor and all its signaling in a balanced manner, whilst IGF-1R targeting by small molecule Nutlin-3 parallels receptor degradation with a transient biased pERK1/2 activity, with both strategies synergizing with MEK1/2 inhibition. On the other hand, IGF-1R down-regulation by a targeted antibody (Figitumumab) induces a biased receptor conformation, preserved even when the receptor is exposed to the balanced natural ligand IGF-1. This process sustains MAPK activity and competes with the MEK1/2 inhibition. Our results indicate that IGF-1R down-regulation offers an approach to increase the sensitivity of melanoma cells to MAPK inhibition, and highlights that controlling biased signaling could provide greater specificity and precision required for multi-hit therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.