Targeting SRC in glioblastoma tumors and brain metastases: rationale and preclinical studies.
Glioblastoma (GBM) is an extremely aggressive, infiltrative tumor with a poor prognosis. The regulatory approval of bevacizumab for recurrent GBM has confirmed that molecularly targeted agents have potential for GBM treatment. Preclinical data showing that SRC and SRC-family kinases (SFKs) mediate intracellular signaling pathways controlling key biologic/oncogenic processes provide a strong rationale for investigating SRC/SFK inhibitors, e.g., dasatinib, in GBM and clinical studies are underway. The activity of these agents against solid tumors suggests that they may also be useful in treating brain metastases. This article reviews the potential for using SRC/SFK inhibitors to treat GBM and brain metastases.
Cleveland Clinic Main Campus, Cleveland, OH 44195, USA. ahluwam@ccf.org
Manmeet S
MS
Ahluwalia
John
J
de Groot
Wei Michael
WM
Liu
Candece L
CL
Gladson
D001932:Brain Neoplasms / Q000378:metabolism* / Q000517:prevention & control / Q000556:secondary; D049109:Cell Proliferation / Q000187:drug effects; D000069439:Dasatinib; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000627:therapeutic use; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D016392:Proto-Oncogene Proteins pp60(c-src); D019061:src-Family Kinases; D000069439:Dasatinib