Molecular targets for emerging anti-tumor therapies for neurofibromatosis type 1.
Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome. NF1 patients present with a constellation of clinical manifestations and have an increased risk of developing certain benign and malignant tumors. This disease results from mutation within the gene encoding neurofibromin, a GTPase activating protein (GAP) for Ras. Functional loss of this protein compromises Ras inactivation, which leads to the aberrant growth and proliferation of neural crest-derived cells and, ultimately, tumor formation. Current management of NF1-associated malignancy involves radiation, surgical excision, and cytotoxic drugs. The limited success of these strategies has fueled researchers to further elucidate the molecular changes that drive tumor formation and progression. This discussion will highlight how intracellular signaling molecules, cell-surface receptors, and the tumor microenvironment constitute potential therapeutic targets, which may be relevant not only to NF1-related malignancy but also to other human cancers.
Dilworth
Joshua T
JT
Department of Pharmacology, Wayne State University, Detroit, MI, USA.
Kraniak
Janice M
JM
Wojtkowiak
Jonathan W
JW
Gibbs
Richard A
RA
Borch
Richard F
RF
Tainsky
Michael A
MA
Reiners
John J
JJ
Mattingly
Raymond R
RR
D000818:Animals; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016514:Genes, Neurofibromatosis 1; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000378:metabolism; D025542:Neurofibromin 1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
D025542:Neurofibromin 1