Receptor Tyrosine Kinases as Targets for Treatment of Peripheral Nerve Sheath Tumors in NF 1 Patients
Abstract
The purpose of this study is the preclinical testing of multiple available tyrosine kinase inhibitors for NF1-associated benign and malignant tumors in vitro and in vivo. We found frequent copy number changes for EGFR and ERBB2, and also for the tumor suppressor genes PTEN, CDKN2A and TP53 in MPNST. CDKN2A loss was associated with metastasis. EGFR and ERBB2 were frequently expressed in MPNST on the protein level. MPNST and neurofibroma xenograft mouse models have been established. Erlotinib, and combined AMN107/Gefinitib inhibited cell proliferation in vitro. In the xenograft model, Gefinintib and Glivec suppressed growth of the xenograft tumors. Glivec treatment led also to shrinkage of plexiform neurofibromas xenograft in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA482237
Entities
People
- Victor-felix Mautner