10-20% of GBM patients respond to EGFR kinase inhibitors. Surprisingly, studies on tumor samples from this patient population failed to reveal mutations in the EGFR kinase domain. This suggests that an unidentified biomarker(s) in GBM determine patient response to EGFR kinase inhibitors.

INNOVATION:  UCLA scientists recently determined the underlying cause of EGFR kinase inhibitor resistance in GBM. Patients with malignant glioma were treated with EGFR kinase inhibitors and classified as either responders (>25% tumor shrinkage) or non-responders (>25% tumor growth). Responders had 5.6 times greater median time to progression than non-responders (290 days vs. 52 days, respectively). Parsing of the data revealed the expression of two particular genes in the responder group while non-responders failed to express these same genes. Patients expressing only one of the biomarkers also failed to respond significantly to inhibitor therapy, with a median time to progression of 112 days. Further analysis revealed that patients expressing both biomarkers were 51 times more likely to respond to EGFR kinase inhibitors. It was therefore reasoned that the expression of these genes enabled the EGFR kinase inhibitors to have a therapeutic effect on the malignancy. Thus, screening patients with malignant glioma for these biomarkers may identify candidates for EGFR kinase inhibitor therapy.

POTENTIAL APPLICATIONS 

• The identified biomarkers can be used as a molecular predictor of clinical response in patients with GBM, and possibly other malignancies as well.
• The discovery of the biomarkers suggests the potential for combining EGFR kinase inhibitors with other clinical therapeutics.

ADVANTAGES

• The biomarkers allow for the identification of GBM patients most likely to respond to EGFR kinase inhibitors.

Reference: UCLA Case No. 2005-452

PCT Application: WO/06/116016