A discovery by Van Andel Research Institute (VARI) scientists enables the prediction of patient sensitivity to proposed drug therapies for glioblastoma.
The study investigated glioblastoma models characterized by cell signaling activation and gene amplification for their susceptibility to inhibitors of both the human MET oncogene and the epidermal growth factor receptor (EFGR).
In tumor cells, oncogenes are often mutated or expressed at high levels. High MET levels often occur in human tumors, and cells with inappropriate MET signaling produce activity that potently affects the spread of cancer. The signaling is implicated in most types of human cancers and high MET expression often correlates with poor prognosis. Mutations affecting EGFR expression or activity are also linked to cancer.
“Because oncogene MET and EGFR inhibitors are in clinical development against several types of cancer, including glioblastoma, it is important to identify predictive markers that indicate patient subgroups suitable for such therapies,” says VARI research scientist Qian Xie, PhD.
“Studies have shown that targeting MET signaling can have potent antitumor effects,” says George F. Vande Woude, PhD, head of the VARI Laboratory of Molecular Oncology. “It is important to understand the mechanisms leading to HGF/MET sensitivity and to identify the patient subgroups most likely to benefit from MET-targeted therapeutics.”
Because MET and HGF play an integral role in the process of cell survival, growth, blood vessel formation, and metastasis, they are a significant target in the development of anti-cancer drugs. “Progress in understanding this vital process has led to the successful development of blocking antibodies and a large number of small-molecule MET kinase inhibitors,” says Vande Woude. “Results from recent clinical studies demonstrate that inhibiting MET signaling in several types of solid human tumors has major therapeutic value.”
The study was published in the Proceedings of the National Academy of Science.
Release Date: Feb. 6, 2012
Source: Van Andel Research Institute