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| Critical update and emerging trends in epidermal growth factor receptor targeting in cancer |
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| Author(s): Baselga J, Arteaga CL |
| Source: JOURNAL OF CLINICAL ONCOLOGY Volume: 23 Issue: 11 Pages: 2445-2459 Published: APR 10 2005 |
| Times Cited: 289 References: 133 |
| Abstract: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB receptor family that is abnormally activated in many epithelial tumors. The aberrant activation of the EGFR leads to enhanced proliferation and other tumor-promoting activities, which provide a strong rationale to target this receptor family. There are two classes of anti-EGFR agents: monoclonal antibodies (MAbs) directed at the extracellular domain of the receptor and small molecule, adenosine triphosphate-competitive inhibitors of the receptor's tyrosine kinase. Anti-EGFR MAbs have shown antitumor activity in advanced colorectal carcinoma, squamous cell carcinomas of the head and neck, non-small-cell lung cancer (NSCLC) and renal cell carcinomas. The tyrosine kinase inhibitors (TKIs) have a partially different activity profile. They are active against NSCLC, and a specific EGFR inhibitor has shown improvement in survival. Recently, mutations and amplifications of the EGFR gene have been identified in NSCLC and predict for enhanced sensitivity to anti-EGFR TKIs. In addition to specific anti-EGFR TKIs, there are broader acting inhibitors such as dual EGFR HER-2 inhibitors and combined anti-pan-ErbB and antivascular endothelial growth factor receptor inhibitors. Current research efforts are directed at selecting the optimal dose and schedule and identifying predictive factors of response and resistance beyond EGFR gene mutations and/or amplifications. Finally, there is a need for improved strategies to integrate anti-EGFR agents with conventional therapies and to explore combinations with other molecular targeted approaches including other antireceptor therapies, receptor-downstream signaling transduction inhibitors, and targeted approaches interfering with other essential drivers of cancer, such as angiogenesis. |
| Document Type: Review |
| Language: English |
| Reprint Address: Baselga, J (reprint author), Vall Hebron Res Inst, Med Oncol Serv, Paseo Vall Hebron 119-129, Barcelona 08035, Spain |
Addresses:
1. Vall Hebron Res Inst, Med Oncol Serv, Barcelona 08035, Spain
2. Vall Hebron Univ Hosp, Barcelona 08035, Spain
3. Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA
4. Vanderbilt Ingram Canc Ctr, Dept Canc Biol, Nashville, TN USA
5. Vanderbilt Ingram Canc Ctr, Breast Canc Program, Nashville, TN USA |
| Publisher: AMER SOC CLINICAL ONCOLOGY, 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA |
| Subject Category: Oncology |
| IDS Number: 915OI |
| ISSN: 0732-183X |
| DOI: 10.1200/JCO.2005.11.890 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |