Epidermal Growth Factor Receptor Family

Epidermal Growth Factor Receptor

The epidermal growth factor (EGF) pathway has been identified as a key regulator of cell growth and replication (30,31). Cumulative evidence shows that the epidermal growth factor receptor (EGFR) pathway is actively involved in a wide variety of solid tumurs, including non-small cell lung cancer (NSCLC), prostate cancer, breast cancer, stomach cancer, colon cancer, ovarian cancer, and tumors of the head and neck (30-32). Overexpression of the EGFR in cancer cells has been associated with more advanced disease, development of metastatic phenotypes, and poor prognosisents (32). Iressa™, a new tyro-sine kinase inhibitor, directly blocks the signals for cell growth and division and is currently licensed for the treatment of inoperable or recurrent NSCLC in Asia and is being tested in clinical trials for other solid tumors (33). Other drugs targeting the EGFR are Tarceva™ and Erbitux™, which are currently in clinical trials.

HER2 / neu

HER2/neu has been shown to be overexpressed in 20% to 30% of breast cancer patients (34,35). Recent evidence supports a clear association between HER2 overexpression and reduced overall and disease-free survival, especially in patients with node-positive disease (34-38). Tumors displaying HER2 amplification show a correlation with poor prognosis (39,40). Thus, the greatest value of HER2 as a predictive marker lies in the prediction of response to therapies that target HER2, notably herceptin. Indeed, patients with strongly HER2-positive breast cancer get significant clinical benefits from herceptin therapy, and HER2 testing has become an integral part of the optimal management of breast cancer patients. It is important to determine HER2 status of all primary breast cancers at the time of diagnosis and recurrence because HER2 overexpression and amplification can be used to identify patients for herceptin therapy (41). Thus, HER2 has approached a clinically validated status as a prognostic factor and also as a predictive factor for response to therapy, and it is already part of the routine assessment for breast cancer patients. A prior knowledge of HER2 status is therefore an absolute requirement for herceptin therapy.

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