Patients with
Neurofibromatosis type 1 (NF1) and
Neurofibromatosis type 2 (NF2) are predisposed to
tumors of the nervous system. NF1 patients predominantly develop
neurofibromas, and
Malignant Peripheral Nerve Sheath Tumors (
MPNST) while NF2 patients develop
schwannomas and
meningiomas. Here we quantified the drug sensitivities of NF1 and NF2 tumor cell lines in a high throughput platform. The platform contained a comprehensive collection of inhibitors of
MEK, RAF, RAS, farnesyl
transferase, PAK and ERK, representative drugs against many other
cancer pathways including Wnt, Hedgehog, p53,
EGF, HDAC, as well as classical
cytotoxic agents recommended for treating
MPNST, such as
doxorubicin and
etoposide. We profiled seven NF1-associated
MPNST cell lines (ST88-14, ST88-3, 90-8, sNF02.2, T265, S462TY, SNF96.2), one sporadic
MPNST cell line (STS26), one
schwannoma from a NF2 patient (HEI193), one NF2-deficient malignant
meningioma (KT21-MG-Luc5D), one mouse NF2
schwannoma (SC4) and one sporadic rat
schwannoma (RT4-67 or RT4). NF1 cells were primarily distinguished from NF2 cells and the sporadic
MPNST cell line by their sensitivity to
MEK and ERK inhibitors, and to a smaller extent their sensitivity to BH3 mimetics and farnesyl
transferase inhibitors. The platform was highly successful in predicting the effects of clinical trials for
Neurofibromas.