Journal
CANCER AND METASTASIS REVIEWS
Volume 29, Issue 1, Pages 37-48Publisher
SPRINGER
DOI: 10.1007/s10555-010-9201-z
Keywords
Epidermal growth factor receptor; NSCLC; Targeted therapy; Resistance
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Funding
- Boehringer Ingelheim Pharmaceuticals, Inc (BIPI)
- Early Detection Research Network
- University of Texas SPORE
- BIPI
- NATIONAL CANCER INSTITUTE [P50CA070907] Funding Source: NIH RePORTER
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Non-small cell lung cancer (NSCLC) is the major cause of cancer-related deaths in the USA and worldwide. Most patients present with advanced disease, and treatment options for these patients are generally limited to platinum-based chemotherapy and a few targeted therapies. Targeted agents currently in use for NSCLC inhibit oncogenic receptor tyrosine kinase pathways, such as the epidermal growth factor receptor (EGFR) pathway. While current EGFR-targeted agents, including erlotinib and gefitinib, may result in dramatic responses, they demonstrate efficacy in only a fraction of patients, and resistance to these agents frequently develops. In order to select patients most likely to benefit from blockade of EGFR pathways, investigators have focused on identifying molecular correlates of response to anti-EGFR therapy. New strategies to minimize the risk of resistance to EGFR inhibition have been employed in the development of next-generation EGFR tyrosine kinase inhibitors, such as PF00299804 and BIBW 2992; these include irreversibility of target binding, inhibition of multiple EGFR family receptors, and/or simultaneous inhibition of EGFR and other oncogenic pathways.
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