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Anti-cancer therapy with EGFR inhibitors: factors of prognostic and predictive significance.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Metro, Giulio Finocchiaro, Giovanna Cappuzzo, Federico |
| Copyright Year | 2006 |
| Abstract | The epidermal growth factor receptor (EGFR) pathway plays an important role in development and progression of many human malignancies, including non-small cell lung cancer (NSCLC). Several new molecules inhibiting this critical biological pathway have been synthesized and tested in clinical trials, including small tyrosine-kinase inhibitors (TKIs), such as gefitinib and erlotinib, and monoclonal antibodies, such as cetuximab. To this regard, emerging data suggest that patients with the highest chance of responding to TKIs should be selected on the basis of clinical and, most of all, biological characteristics. In fact, recent studies showed that NSCLC patients with increased EGFR gene copy number or with activating mutations of the EGFR catalytic domain which also present Akt activation or HER2 gene gain, have a better outcome than patients without these features. Interestingly, new predictors of response in tumors other than NSCLC are also being progressively highlighted. Although biological markers of sensitivity may differ for each form of malignancy, they invariably depend on the degree of activation of the EGFR pathway and on the importance that EGFR signalling holds as oncogenic determinant of a specific type of cancer. Prospective trials are warranted to validate criteria for selection of patient selection for EGFR-inhibitors. The Epidermal Growth Factor Receptor (EGFR) family is a group of four receptors including EGFR (Erb-B1), HER2/neu (Erb-B2), HER3 (Erb-B3) and HER4 (Erb-B4) [1]. The rationale for developing drugs targeting the EGFR is based on the evidence that this receptor, commonly expressed primarily in non-malignant cells of epithelial origin, is implicated in proliferation and survival of a number of tumors in which its over-expression appears to be related to poor prognosis and resistance to chemoand/or radiotherapy [2]. So far, several drugs interfering with the EGFR have been synthesized. Among these, small molecules tyrosine kinase inhibitors (TKIs), such as gefitinib (Iressa) and erlotinib (Tarceva), or cetuximab (Erbitux), a monoclonal antibody directed against the extracellular domain of the EGFR, have been tested in preclinical and clinical models, especially in non-small cell lung cancer (NSCLC). |
| Starting Page | 28 |
| Ending Page | 41 |
| Page Count | 14 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/annonc/17/suppl_2/10.1093/annonc/mdj920/2/mdj920.pdf?Expires=1492609510&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=cUwpMh57rWSpzC6qyq1ga7n4TKdPetVE7Tg7pQXx8SbkrL1NgAcYLjpoGWO96WBsQULnCton5ujZQiED6biVpH0W3IC1nJjXZjzkCWBdUfSS8PngdWzyCaFyU1rwp2Wi~ZKKy1qKXFrgszK1XsEdtVbFAS0wVNQxswvqP~hG4Suiq6z5YmsmN6~iIjo0bfAiHe-RP-MqH2nkj1XbiYvFogmhciLWPsVLgOqDeXjS3xGzUh3PphqhzAsx94GW9a36jJSmPsFdYrENhssFPOB3TDWe35WMdWXIFxgw-U2UZxcl9B5cnEEbmOFENcIfq4h1GIi3v3Bb6qYdRhlrID4zUA__ |
| PubMed reference number | 16608980v1 |
| Volume Number | 17 |
| Journal | Annals of oncology : official journal of the European Society for Medical Oncology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Biomarkers, Tumor Catalytic Domain Copy Number Coxsackievirus B4 Ab:Titr:Pt:Ser:Qn Drug Delivery Systems EGFR gene ERBB4 wt Allele ESR2 wt Allele Growth Factor Receptors Monoclonal Antibodies Mutation Neoplasms Non-Small Cell Lung Carcinoma Patients Protein Tyrosine Kinase Proto-Oncogene Proteins c-akt Small Molecule Small cell carcinoma of lung Tyrosine Kinase Inhibitors [MoA] biological signaling cellular targeting cetuximab erlotinib gefitinib |
| Content Type | Text |
| Resource Type | Article |
