title: Targeting SH2 domains in breast cancer.
abstract: Breast cancer is among the most commonly diagnosed cancer types in women worldwide and is the second leading cause of cancer-related disease in the USA. SH2 domains recruit signaling proteins to phosphotyrosine residues on aberrantly activated growth factor and cytokine receptors and contribute to cancer cell cycling, metastasis, angiogenesis and so on. Herein we review phosphopeptide mimetic and small-molecule approaches targeting the SH2 domains of Grb2, Grb7 and STAT3 that inhibit their targets and reduce proliferation in in vitro breast cancer models. Only STAT3 inhibitors have been evaluated in in vivo models and have led to tumor reduction. Taken together, these studies suggest that targeting SH2 domains is an important approach to the treatment of breast cancer.
authors.affiliation: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Pietro
authors.initials: P
authors.lastname: Morlacchi
authors.forename: Fredika M
authors.initials: FM
authors.lastname: Robertson
authors.forename: Jim
authors.initials: J
authors.lastname: Klostergaard
authors.forename: John S
authors.initials: JS
authors.lastname: McMurray
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D051380:GRB2 Adaptor Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051382:GRB7 Adaptor Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D018909:src Homology Domains
chemical_list: D051380:GRB2 Adaptor Protein; D010748:Phosphopeptides; D050796:STAT3 Transcription Factor; D054852:Small Molecule Libraries; D051382:GRB7 Adaptor Protein