IGF1R Is a Potential New Therapeutic Target for HGNET-BCOR Brain Tumor Patients.
Int J Mol Sci
; 20(12)2019 Jun 21.
Article
in En
| MEDLINE
| ID: mdl-31234291
ABSTRACT
(1) Background:
The high-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a highly malignant tumor. Preclinical models and molecular targets are urgently required for this cancer. Previous data suggest a potential role of insulin-like growth factor (IGF) signaling in HGNET-BCOR. (2)Methods:
The primary HGNET-BCOR cells PhKh1 were characterized by western blot, copy number variation, and methylation analysis and by electron microscopy. The expression of IGF2 and IGF1R was assessed by qRT-PCR. The effect of chemotherapeutics and IGF1R inhibitors on PhKh1 proliferation was tested. The phosphorylation of IGF1R and downstream molecules was assessed by western blot. (3)Results:
Phkh1 cells showed a DNA methylation profile compatible with the DNA methylation class "HGNET-BCOR" and morphologic features of cellular cannibalism. IGF2 and IGF1R were highly expressed by three HGNET-BCOR tumor samples and PhKh1 cells. PhKh1 cells were particularly sensitive to vincristine, vinblastine, actinomycin D (IC50 < 10 nM for all drugs), and ceritinib (IC50 = 310 nM). Ceritinib was able to abrogate the proliferation of PhKh1 cells and blocked the phosphorylation of IGF1R and AKT. (4)Conclusion:
IGF1R is as an attractive target for the development of new therapy protocols for HGNET-BCOR patients, which may include ceritinib and vinblastine.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrimidines
/
Sulfones
/
Vinblastine
/
Brain Neoplasms
/
Receptors, Somatomedin
/
Neoplasms, Neuroepithelial
/
Antineoplastic Agents
Type of study:
Guideline
/
Prognostic_studies
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Int J Mol Sci
Year:
2019
Type:
Article
Affiliation country:
Germany