Lack of somatic ErbB2 tyrosine kinase domain mutations in hepatocellular carcinoma
Aim: Small molecules targeting the epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain have shown promising activity in cancer therapeutics. Recent reports suggest activity of erlotinib, an ErbB1 inhibitor, and lapatinib, a dual inhibitor of ErbB1 and ErbB2, in hepatocellul...
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| Published in: | Hepatology research Vol. 38; no. 8; pp. 838 - 841 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
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Melbourne, Australia
Blackwell Publishing Asia
01-08-2008
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| Abstract | Aim: Small molecules targeting the epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain have shown promising activity in cancer therapeutics. Recent reports suggest activity of erlotinib, an ErbB1 inhibitor, and lapatinib, a dual inhibitor of ErbB1 and ErbB2, in hepatocellular carcinoma (HCC). Activating ErbB1 somatic mutations may predict treatment responses.
Method and Results: We have previously reported ErbB1 tyrosine kinase domain mutations to be rare or absent in HCC, but data on the frequency of ErbB2 tyrosine kinase domain mutations in HCC is currently limited, apart from reports of a missense mutation identified in 11% of a small Caucasian sample. We studied exons 18–23 of the ErbB2 gene from tumor DNA of 100 Asian human HCC and found no exonic mutations of potential significance.
Conclusion: Alternative mechanisms may be responsible for the observed therapeutic efficacy of ErbB1 and ErbB2 tyrosine kinase inhibitors. |
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| AbstractList | AIMSmall molecules targeting the epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain have shown promising activity in cancer therapeutics. Recent reports suggest activity of erlotinib, an ErbB1 inhibitor, and lapatinib, a dual inhibitor of ErbB1 and ErbB2, in hepatocellular carcinoma (HCC). Activating ErbB1 somatic mutations may predict treatment responses. METHOD AND RESULTSWe have previously reported ErbB1 tyrosine kinase domain mutations to be rare or absent in HCC, but data on the frequency of ErbB2 tyrosine kinase domain mutations in HCC is currently limited, apart from reports of a missense mutation identified in 11% of a small Caucasian sample. We studied exons 18-23 of the ErbB2 gene from tumor DNA of 100 Asian human HCC and found no exonic mutations of potential significance. CONCLUSIONAlternative mechanisms may be responsible for the observed therapeutic efficacy of ErbB1 and ErbB2 tyrosine kinase inhibitors. Small molecules targeting the epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain have shown promising activity in cancer therapeutics. Recent reports suggest activity of erlotinib, an ErbB1 inhibitor, and lapatinib, a dual inhibitor of ErbB1 and ErbB2, in hepatocellular carcinoma (HCC). Activating ErbB1 somatic mutations may predict treatment responses. We have previously reported ErbB1 tyrosine kinase domain mutations to be rare or absent in HCC, but data on the frequency of ErbB2 tyrosine kinase domain mutations in HCC is currently limited, apart from reports of a missense mutation identified in 11% of a small Caucasian sample. We studied exons 18-23 of the ErbB2 gene from tumor DNA of 100 Asian human HCC and found no exonic mutations of potential significance. Alternative mechanisms may be responsible for the observed therapeutic efficacy of ErbB1 and ErbB2 tyrosine kinase inhibitors. Aim: Small molecules targeting the epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain have shown promising activity in cancer therapeutics. Recent reports suggest activity of erlotinib, an ErbB1 inhibitor, and lapatinib, a dual inhibitor of ErbB1 and ErbB2, in hepatocellular carcinoma (HCC). Activating ErbB1 somatic mutations may predict treatment responses. Method and Results: We have previously reported ErbB1 tyrosine kinase domain mutations to be rare or absent in HCC, but data on the frequency of ErbB2 tyrosine kinase domain mutations in HCC is currently limited, apart from reports of a missense mutation identified in 11% of a small Caucasian sample. We studied exons 18–23 of the ErbB2 gene from tumor DNA of 100 Asian human HCC and found no exonic mutations of potential significance. Conclusion: Alternative mechanisms may be responsible for the observed therapeutic efficacy of ErbB1 and ErbB2 tyrosine kinase inhibitors. Aim: Small molecules targeting the epidermal growth factor receptor (EGFR) intracellular tyrosine kinase domain have shown promising activity in cancer therapeutics. Recent reports suggest activity of erlotinib, an ErbB1 inhibitor, and lapatinib, a dual inhibitor of ErbB1 and ErbB2, in hepatocellular carcinoma (HCC). Activating ErbB1 somatic mutations may predict treatment responses. Method and Results: We have previously reported ErbB1 tyrosine kinase domain mutations to be rare or absent in HCC, but data on the frequency of ErbB2 tyrosine kinase domain mutations in HCC is currently limited, apart from reports of a missense mutation identified in 11% of a small Caucasian sample. We studied exons 18–23 of the ErbB2 gene from tumor DNA of 100 Asian human HCC and found no exonic mutations of potential significance. Conclusion: Alternative mechanisms may be responsible for the observed therapeutic efficacy of ErbB1 and ErbB2 tyrosine kinase inhibitors. |
| Author | Guo, Jia-Yi Lee, Soo-Chin Yap, Hui-Ling Goh, Boon-Cher Lim, Seng-Gee Wong, Chiung-Ing |
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| Cites_doi | 10.1186/1471-2407-6-278 10.3748/wjg.v11.i9.1382 10.1056/NEJMoa040938 10.1016/j.canlet.2006.05.018 10.1097/01.fpc.0000184959.82903.02 10.1056/NEJMoa050753 10.1158/1078-0432.CCR-05-0926 10.1126/science.1099314 10.1002/cncr.22886 10.1056/NEJMoa050736 10.1158/0008-5472.CAN-05-1182 10.1200/JCO.2005.14.696 10.1200/jco.2006.24.18_suppl.4010 |
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| References_xml | – volume: 23 start-page: 6657 year: 2005 end-page: 63 article-title: Phase II study of Erlotinib (OSI‐774) in patients with advanced hepatocellular cancer publication-title: JCO – volume: 66 start-page: 1630 year: 2006 end-page: 9 article-title: Activity of the dual kinase inhibitor lapatinib (GW 572016) against Her‐2 overexpressing and trastuzumab‐treated breast cancer cells publication-title: Cancer Res – volume: 353 start-page: 123 year: 2005 end-page: 32 article-title: Erlotinib in previously treated non‐small‐cell lung cancer publication-title: N Engl J Med – volume: 25 year: 2007 article-title: Sorafenib improves survival in advanced Hepatocellular Carcinoma (HCC): results of a Phase III randomized placebo‐controlled trial (SHARP) trial) publication-title: J Clin Oncol – volume: 6 start-page: 278 year: 2006 article-title: Intragenic EGFR and EGFR2 mutations in hepatobiliary tumors and potential role in predicting response to agents that target EGFR publication-title: BMC Cancer – volume: 11 start-page: 1382 year: 2005 end-page: 6 article-title: Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma publication-title: World J Gastroenterol – volume: 353 start-page: 133 year: 2005 end-page: 44 article-title: Erlotinib in lung cancer – molecular and clinical predictors of outcome publication-title: N Engl J Med – volume: 16 start-page: 73 year: 2006 end-page: 74 article-title: Lack of somatic mutations in EGFR tyrosine kinase domain in hepatocellular and nasopharyngeal carcinoma publication-title: Pharmacogenet Genomics – volume: 24 start-page: 4010 year: 2006 article-title: Phase II study of lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase 1 and 2 (Her2/Neu) in patients (pts) with advanced biliary tree cancer (BTC) or hepatocellular cancer (HCC). A California Consortium (CCC‐P) Trial publication-title: J Clin Oncol – volume: 248 start-page: 32 year: 2007 end-page: 40 article-title: Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma publication-title: Cancer Lett – volume: 304 start-page: 1497 year: 2004 end-page: 500 article-title: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy publication-title: Science – volume: 350 start-page: 2129 year: 2004 end-page: 39 article-title: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non‐small‐cell lung cancer to gefitinib publication-title: N Engl J Med – volume: 11 start-page: 8105 year: 2005 end-page: 8 article-title: Response of some head and neck cancers to epidermal growth factor receptor tyrosine kinase inhibitors may be linked to mutation of ERBB2 rather than EGFR publication-title: Clin Cancer Res – volume: 110 start-page: 1059 year: 2007 end-page: 67 article-title: Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma publication-title: Cancer – ident: e_1_2_5_13_2 doi: 10.1186/1471-2407-6-278 – ident: e_1_2_5_8_2 doi: 10.3748/wjg.v11.i9.1382 – ident: e_1_2_5_4_2 doi: 10.1056/NEJMoa040938 – ident: e_1_2_5_7_2 doi: 10.1016/j.canlet.2006.05.018 – ident: e_1_2_5_14_2 doi: 10.1097/01.fpc.0000184959.82903.02 – ident: e_1_2_5_2_2 doi: 10.1056/NEJMoa050753 – ident: e_1_2_5_6_2 doi: 10.1158/1078-0432.CCR-05-0926 – ident: e_1_2_5_15_2 doi: 10.1126/science.1099314 – ident: e_1_2_5_10_2 doi: 10.1002/cncr.22886 – ident: e_1_2_5_5_2 doi: 10.1056/NEJMoa050736 – volume: 25 year: 2007 ident: e_1_2_5_12_2 article-title: Sorafenib improves survival in advanced Hepatocellular Carcinoma (HCC): results of a Phase III randomized placebo‐controlled trial (SHARP) trial) publication-title: J Clin Oncol contributor: fullname: Llover J – ident: e_1_2_5_3_2 doi: 10.1158/0008-5472.CAN-05-1182 – ident: e_1_2_5_9_2 doi: 10.1200/JCO.2005.14.696 – volume: 24 start-page: 4010 year: 2006 ident: e_1_2_5_11_2 article-title: Phase II study of lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase 1 and 2 (Her2/Neu) in patients (pts) with advanced biliary tree cancer (BTC) or hepatocellular cancer (HCC). A California Consortium (CCC‐P) Trial publication-title: J Clin Oncol doi: 10.1200/jco.2006.24.18_suppl.4010 contributor: fullname: Ramanathan RK |
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| Title | Lack of somatic ErbB2 tyrosine kinase domain mutations in hepatocellular carcinoma |
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