Authors' recommendations: It is estimated that lung cancer was diagnosed in more than 220,000 Americans in 2011, and that nearly 157,000 died from the disease, making lung cancer the leading cause of cancer-related deaths in the United States. Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancers and includes squamous cell carcinomas, adenocarcinomas, and large cell carcinomas of the lung. In general, NSCLC responds poorly to standard chemotherapy and radiation treatment regimens, which is reflected in a 5-year survival rate of only 14%. Newer treatments for NSCLC include targeted therapies, or the use of medications that target specific proteins involved in tumor growth and progression, such as the epidermal growth factor receptor (EGFR). EGFR is a transmembrane tyrosine kinase receptor of the ErbB family that, when activated, triggers downstream signaling cascades that play a role in the regulation of cell growth, proliferation, differentiation, and survival. Because of its involvement in signaling cascades known to be dysregulated in a variety of malignancies (including lung cancer), EGFR has been an important target for the development of such medications. Several EGFR tyrosine kinase inhibitors (TKIs) have been developed and are designed to prevent the activation of EGFR, thereby inhibiting receptor tyrosine kinase activity and downstream signaling cascades. Erlotinib and gefitinib are EGFR TKIs used in NSCLC patients who have failed at least one prior chemotherapy regimen. However, the effectiveness of these medications appears to be limited to 10% to 30% of treated patients. This response rate has led to the search for predictive biomarkers to help identify patients who are more likely to benefit from these medications. Investigated biomarkers that may help predict TKI efficacy include the presence of EGFR gene variants, EGFR gene amplification, and the presence of Kirsten rat sarcoma viral oncogene (KRAS) sequence variants. More recently, the VeriStrat® test was developed to identify patients most likely to respond to EGFR TKI therapy. The assay utilizes mass spectrometry, a technique that analyzes the mass-to-charge ratio of charged particles, to characterize the protein profile of pretreatment serum from NSCLC patients who are candidates for EGFR TKI therapy. A classification algorithm is then used to categorize patients according to the likelihood of treatment response. The proteins represented in the profile have not been characterized, but it is believed that the protein expression pattern represents the inappropriate activation of signaling cascades downstream of EGFR, resulting in a resistance to anti-EGFR therapies (including EGFR TKIs).

Project Status: Completed

Year Published: 2012

URL for published report: http://www.hayesinc.com/hayes/crd/?crd=13553

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

Contact Name: saleinfo@hayesinc.com

Contact Email: saleinfo@hayesinc.com

Copyright: 2011 Winifred S. Hayes, Inc