The EGFR (or HER1) signaling pathway is a promising and widely studied interventional target.  EGFR signaling involves a cascade of chemical reactions that serve to drive cell behaviors.  In a healthy cell, EGFR signaling helps to perform a variety of useful functions such as regulating normal cell growth, facilitating wound healing, and helping to resist damage from toxins.  However, abnormal  signaling along the EGFR pathway has been associated with numerous dangerous cell behaviors such as tumor growth and progression, metastasis, resistance to chemotherapy, and generally poorer patient prognosis.  Because of the high cost of anti-EGFR drugs and the fact that only a relatively small percentage of patients benefit from them - about 10% in most studies - there is great urgency to develop laboratory tests that identify patients who are good candidates for anti-EGFR treatments. 

 

Three types of tests have been studied most extensively.  These include tests that measure EGFR protein expression, a test for EGFR gene amplification, and a test for EGFR-related gene mutations.  The EGFR gene amplification test is the only one of the three approaches shown to date to predict for improved survival among patients who receive anti-EGFR drugs.  However, questions concerning this approach remain unanswered and even the principal developer of the test says that it is still too early to recommend his test for routine use.  In one retrospective study of the gene mutation approach, a certain mutation was associated with a modest survival benefit from anti-EGFR treatment, particularly in Asian patients, who seem to have higher incidences of that particular EGFR mutation.  However, a follow-up study failed to reproduce the results.  EGFR protein expression tests have not been shown to correlate reliably either with response or survival.  The Medical Director of Genzyme, a laboratory company that markets a gene-based EGFR test, has stated that a panel consisting of several different tests that collectively assess several, different factors probably will be necessary for meaningful patient selection. 

 

Dr. Weisenthal has developed an approach which is based upon the Functional Tumor Cell Profiling method.  In a study of 60 non-small lung cancer cell patients, Dr. Weisenthal’s test, which we have named the EGFRx™ Assay, prospectively identified patients who not only responded to gefitinib (Iressa®) and erlotinib (Tarceva®) but who also achieved significantly longer survival periods than patients whose tumors were resistant in vitro to treatment with EGFR-based therapies.  The extent of the survival advantage among patients prospectively identified as likely candidates for anti-EGFR therapy in Dr. Weisenthal’s EGFRx™ assay greatly exceeds that which has been published to date for any other EGFR-related test.  Importantly, patients who were resistant in the EGFRx™ assay but who received anti-EGFR therapy in spite of their negative assay results lived no longer than patients who did not receive anti-EGFR therapy.   Dr. Weisenthal’s findings were presented at the 2006 American Society of Clinical Oncology (ASCO) annual international meeting (click here).  The EGFRx™ assay is applicable to all patients and does not require a panel of different tests such as that predicted by Genzyme.  Once again, this demonstrates the advantage of the Functional Tumor Cell Profiling approach, which evaluates drug activity in the whole cell, as opposed to individually assessing some number of individual of surrogate markers, as in molecular tests, each of which provides only one piece of the puzzle.