Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy.
Growth factor receptor-bound 2 (Grb2) is a ubiquitously expressed adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. As such, it has been implicated in the oncogenesis of several important human malignancies. In addition to this function, research over the last decade has revealed other fundamental roles for Grb2 in cell motility and angiogenesis--processes that also contribute to tumor growth, invasiveness and metastasis. This functional profile makes Grb2 a high priority target for anti-cancer drug development. Knowledge of Grb2 protein structure, its component Src homology domains and their respective structure-function relationships has facilitated the rapid development of sophisticated drug candidates that can penetrate cells, bind Grb2 with high affinity and potently antagonize Grb2 signaling. These novel compounds offer considerable promise in our growing arsenal of rationally designed anti-cancer therapeutics.
Dharmawardana
Pathirage G
PG
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1107, USA.
Peruzzi
Benedetta
B
Giubellino
Alessio
A
Burke
Terrence R
TR
Bottaro
Donald P
DP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D051380:GRB2 Adaptor Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human