MET Protein May Serve as a Biomarker for a Treatment-Resistant Colorectal Cancer Subtype
The MET protein may be a surrogate indicator of the presence of the chemotherapy-resistant epithelial-mesenchymal transition (EMT) subtype of colorectal cancer, a recent study showed.
EMT occurs when epithelial cells change shape and lose cell-to-cell adhesion molecules, thereby allowing the cells to adopt certain characteristics of mesenchymal cells, such as invasiveness and resistance to cell death.
“We want to condense sophisticated gene signatures down to single markers and simple tests that can be used to guide therapy.”
– Dr. Scott Kopetz
Currently, the EMT subtype is identified by its genetic “signature”—multiple gene mutations. However, a single biomarker for this subtype has not been previously identified.
“While we know there are many types of colorectal cancer, we’re not as advanced as we’d like to be in our understanding of them,” said Scott Kopetz, M.D., Ph.D., an associate professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “One of the larger goals of our research is to find simple biomarkers that can be used by doctors in the community to identify subtypes. We want to condense sophisticated gene signatures down to single markers and simple tests that can be used to guide therapy.”
To determine whether MET protein could serve as a biomarker for EMT, Dr. Kopetz and his colleagues compared MET protein expression with the expression of proteins and messenger RNA for genes known to be altered in EMT. The researchers used data from The Cancer Genome Atlas to conduct an exploratory analysis of 139 untreated primary colorectal cancer samples.
Dr. Kopetz and his colleagues found that the expression of MET protein strongly correlated with the expression of the EMT-associated transcription factor Slug and of ERCC1, a marker for oxaliplatin resistance.
No trials as yet, but the pre-clinical work-up is noteworthy.
Google: "Cabozantinib goes 12 for 12 in CRC"
In addition, the lab mice explanted in this study were top-line techno-wonders...
Joeflow and I chatted about this updated mouse explant population a few months ago.
The thread shouldn't be hard to find. Very impressive potential in CRC...
Thanks for the post, biglabowski...
"This drug appears to work by inhibiting angiogenesis – the growth of new blood vessels that tumor tissues need to supply themselves with nutrients. Unlike other drugs that target angiogenesis, XL-184 targets not only the primary driver of angiogenesis, the VEGFR2 signaling pathway, but also targets c-Met, a pathway that is important for survival of tumor cells.
"Other studies have shown that anti-VEGF therapy decreases angiogenesis, but also promotes tumor cell survival and metastasis that is dependent on the c-MET signaling pathway," Arcaroli says. "This drug inhibits both – the formation of blood vessels and a primary escape mechanism whereby tumor cells survive. This two-target approach may be the reason we're seeing very potent effects with this agent."
It's amazing that EXEL still gets no respect; whoever said Wall Street is the street of dreams may have also been referring to nightmares.LOL