Defining clinically relevant molecular subsets of lung cancer Journal Article
| Author: | Pao, W. |
| Article Title: | Defining clinically relevant molecular subsets of lung cancer |
| Abstract: | The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, induce dramatic responses in certain patients with non-small cell lung cancer (NSCLC). As such, the drugs provide an unexpected tool to dissect clinically relevant molecular subsets of NSCLC. For example, using mutational profiling of tumor DNA from patients with sensitivity, primary resistance, and secondary resistance to these agents, we and others have demonstrated that somatic mutations in the tyrosine kinase domain of EGFR are associated with sensitivity to gefitinib and erlotinib, while mutations in KRAS, which encodes a GTPase downstream of EGFR, are associated with primary resistance. Furthermore, second site mutations in the EGFR kinase domain are commonly found in patients with acquired resistance. We are now using a variety of molecular and biological approaches to help further define molecular subsets of lung cancer that have relevance in the clinic. © 2006 Springer-Verlag. |
| Keywords: | human tissue; unclassified drug; gene mutation; human cell; somatic mutation; exon; genetics; mutation; clinical trial; review; erlotinib; nonhuman; conference paper; cancer patient; genetic analysis; protein domain; sensitivity analysis; gastrointestinal stromal tumor; imatinib; protein kinase inhibitor; lung non small cell cancer; lung neoplasms; clinical assessment; epidermal growth factor receptor; genetic association; lung cancer; receptor, epidermal growth factor; drug resistance; drug resistance, neoplasm; protein tyrosine kinase; cancer resistance; tyrosine kinase inhibitors; protein tyrosine kinase inhibitor; protein kinase inhibitors; lung tumor; tumor suppressor gene; drug antagonism; lung adenocarcinoma; dna; drug response; gefitinib; dna fingerprinting; oncogene k ras; genes, ras; cancer classification; molecular biology; quinazolines; drug sensitivity; non-small cell lung cancer; oncogene ras; quinazoline derivative; epidermal growth factor receptor kinase inhibitor; mutations; guanosine triphosphatase; canertinib; pelitinib; cl 387785; hki 272 |
| Journal Title: | Cancer Chemotherapy and Pharmacology |
| Volume: | 58 |
| Issue: | Suppl.1 |
| ISSN: | 0344-5704 |
| Publisher: | Springer |
| Date Published: | 2006-11-01 |
| Start Page: | s11 |
| End Page: | s15 |
| Language: | English |
| DOI: | 10.1007/s00280-006-0310-x |
| PUBMED: | 17093937 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 4 June 2012" - "CODEN: CCPHD" - "Source: Scopus" |
