6533b835fe1ef96bd129f430

RESEARCH PRODUCT

TRTH-08. HIGH GRADE NEUROEPITHELIAL TUMOR OF THE CENTRAL NERVOUS SYSTEM WITH BCOR ALTERATION IS SENSITIVE TO IGF1R INHIBITION

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description

High grade neuroepithelial tumor of the central nervous system with BCOR alteration (CNS HGNET-BCOR) is a recently described new tumor entity which was formerly diagnosed with diverse histological diagnoses, for example as ependymoma. This tumor predominantly affects children and has a dismal prognosis. No standard therapies for this entity exist so far. Recently we described the activation of the Sonic hedgehog (SHH) and the WNT signaling pathway in this tumor and described a primary cell culture (PhKh1) isolated from a skull metastasis of a seven years old patient. We also detected a high expression of IGF2, which is known to be required for SHH signaling in medulloblastoma. IGF2 signals through IGF1R leading to cell growth via the downstream PI3K/Akt pathway. In pediatric brain tumors high expression of IGF2 has been described in ependymoma and may acts as a molecular target. Here we analyzed the expression of IGF2 in our transcriptome data of 12 pediatric brain tumors patients (6 medulloblastoma, 2 glioblastoma, 2 anaplastic astrocytoma, 1 HGNET-BCOR and 1 ependymoma relapse). The highest expression of IGF2 was detected in the HGNET-BCOR and ependymoma samples. The high expression of IGF2 was maintained in the PhKh1 cell line and was similar to the expression detected in a primary cell culture isolated from the ependymoma relapse. Incubation with increasing concentrations of an antibody that blocks IGF1R resulted in a great reduction of the cell proliferation of the PhKh1 cell line but not of an IGF2-negative control cell line. In conclusion, the high expression of IGF2 may be a common feature of HGNET-BCOR and ependymoma and may represent a target for new approaches. Several monoclonal antibodies and TKIs for IGF1R are being tested in preclinical and early phase clinical studies and may become relevant in the management of this new and aggressive tumor entity.