Therapies targeting specific molecular alterations in conjunction to non-targeted therapies are the future of cancer therapeutics. However, initial clinical trial results have been met with limited success, especially in tumors such as Glioblastoma multiforme (GBM) where there is no one-singular molecular alteration in all tumors that can be targeted. Current strategies using antibody based evaluation of these targets in the specimens have fallen short and cannot be readily repeated with biopsies for followup in GBMs. One such highly prevalent target already undergoing clinical evaluation in GBMs is Epidermal Growth Factor Receptor (EGFR). Here we propose novel diagnostic and non-invasive assays on sera and plasma of GBM patients, the techniques and proof-of-principles which we have already published. We believe these assays will facilitate early identification and follow-up of response of GBMs to biological therapies against EGFR. These assays can easily be extended to other biological targets of GBMs and other human cancers.