BACKGROUND: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in human cancers are associated with increased sensitivity to anilinoquinazoline EGFR inhibitors. To our knowledge no data have been reported on EGFR gene mutations in hormone refractory prostate cancer (HRPC). METHODS: Between March 2003 and December 2004, 23 patients with HRPC received 250 mg oral gefitinib daily in addition to antiandrogen plus luteinizing hormone-releasing hormone (LH-RH) analog for at least 2 months or until disease progression. Patients with unresected prostate cancer prospectively underwent trans-rectal biopsy of primary tumor (before starting gefitinib treatment). RESULTS: None of the patients demonstrated PSA or objective response to gefitinib. We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated from 8 HRPC patients. No patient showed EGFR TK domain mutations. CONCLUSIONS: Our results show EGFR mutations did not occur in these patients suggesting that gefitinib is unlikely to be effective in patients with tumors not harboring specific EGFR TK domain. (c) 2007 Wiley-Liss, Inc.
BACKGROUND: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in humancancers are associated with increased sensitivity to anilinoquinazolineEGFR inhibitors. To our knowledge no data have been reported on EGFR gene mutations in hormone refractory prostate cancer (HRPC). METHODS: Between March 2003 and December 2004, 23 patients with HRPC received 250 mg oral gefitinib daily in addition to antiandrogen plus luteinizing hormone-releasing hormone (LH-RH) analog for at least 2 months or until disease progression. Patients with unresected prostate cancer prospectively underwent trans-rectal biopsy of primary tumor (before starting gefitinib treatment). RESULTS: None of the patients demonstrated PSA or objective response to gefitinib. We sequenced exons 18-21 of the EGFR TK domain from genomic DNA isolated from 8 HRPC patients. No patient showed EGFR TK domain mutations. CONCLUSIONS: Our results show EGFR mutations did not occur in these patients suggesting that gefitinib is unlikely to be effective in patients with tumors not harboring specific EGFR TK domain. (c) 2007 Wiley-Liss, Inc.
Authors: Justin M Drake; Nicholas A Graham; Tanya Stoyanova; Amir Sedghi; Andrew S Goldstein; Houjian Cai; Daniel A Smith; Hong Zhang; Evangelia Komisopoulou; Jiaoti Huang; Thomas G Graeber; Owen N Witte Journal: Proc Natl Acad Sci U S A Date: 2012-01-17 Impact factor: 11.205
Authors: Jeffrey Peppercorn; Iuliana Shapira; Deborah Collyar; Teresa Deshields; Nancy Lin; Ian Krop; Hans Grunwald; Paula Friedman; Ann H Partridge; Richard L Schilsky; Monica M Bertagnolli Journal: J Clin Oncol Date: 2010-04-20 Impact factor: 44.544