Monday November 24, 2014   
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TACKLING RESISTANCE TO BEVACIZUMAB THERAPY IN GBMS by Gabriele Bergers

TACKLING RESISTANCE TO BEVACIZUMAB THERAPY IN GBMS

Led by Gabriele Bergers at University of California, San Francisco

Angiogenesis inhibitors targeting the EGF signaling pathay have been FDA-approved for various cancers including glioblastoma multiforme (GBM), one of the most lethal and angiogenic tumors. This has led to the routine use of the anti-EGF antibody bevacizumab in recurrent GBM, conveying substantial improvements in radiographic response, progression-free survival, and uality of life. Despite these encouraging beneficial effects, patients inevitably develop resistance and freuently fail to demonstrate significantly better overall survival. Unlike chemotherapies in hich tumors exhibit resistance due to genetic mutation of drug targets, emerging evidence suggests that tumors bypass anti-angiogenic therapy hile EGF signaling remains inhibited through a variety of mechanisms that are ust beginning to be recognized. Emerging data from various laboratories and the clinic support to maor recurrence patterns that occur during evasive resistance to anti-angiogenic therapy. Either GBM evoke pathays that endorse reneovascularization or tumors become
more proinvasive to propagate and progress ithout the need to satisfactorily reinitiate angiogenesis.The proinvasive groth pattern renders surgical resection unfeasible and imparts detrimental effects. As there are no parameters used yet that ould help to predict ho a patient ill respond to bevacizumab therapy, patients are randomly selected for ne combinatorial trials ith bevacizumab. Based on on our recent results and preliminary data e ill test the proposition that GBM containing EGFR2/Met tumor cells are more prone to an EMT-like behavior and increased invasion. In addditon, e ill evaluate the concept that tumors positive for both receptors still likely benefit from bevacizumab if subected to an upfront combined treatment modalities targeting EGF and Met. This is a timely and highly significant study that ill help to stratify GBM patients prior bevacizumab treatment and open avenues for appropriate combination therapies that are tailored to individual patients.

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