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EGFR, HER2 and VEGF Pathways

Validated Targets for Cancer Treatment

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Abstract

Targeted therapies are rationally designed to interfere with specific molecular events that are important in tumour growth, progression or survival. Several targeted therapies with anti-tumour activity in human cancer cell lines and xenograft models have now been shown to produce objective responses, delay disease progression and, in some cases, improve survival of patients with advanced malignancies. These targeted therapies include cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody; gefitinib and erlotinib, EGFR-specific tyrosine kinase inhibitors; trastuzumab, an anti-human EGFR type 2 (HER2)-related monoclonal antibody; lapatinib, a dual inhibitor of both EGFR- and HER2-associated tyrosine kinases; and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody.

On the basis of preclinical and clinical evidence, EGFR, HER2 and VEGF represent validated targets for cancer therapy and remain the subject of intensive investigation. Both EGFR and HER2 are targets found on cancer cells, whereas VEGF is a target that acts in the tumour microenvironment. Clinical studies are focusing on how to best incorporate targeted therapy into current treatment regimens and other studies are exploring whether different strategies for inhibiting these targets will offer greater benefit. It is clear that optimal use of targeted therapy will depend on understanding how these drugs work mechanistically, and recognising that their activities may differ across patient populations, tumour types and disease stages, as well as when and how they are used in cancer treatment. The results achieved with targeted therapies to date are promising, although they illustrate the need for additional preclinical and clinical study.

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Acknowledgements

Dr Lenz has acted as a consultant for and received honoraria from Pfizer, Genentech, Bristol-Myers Squibb, sanofi-aventis, Imclone, Roche, Novartis and Response-Genetics; he has also received clinical trial support from Roche, Bristol-Myers Squibb, Eisai, Genentech, sanofi-aventis; and participated in advisory boards and speakers bureau for Imclone and Merck KG. Dr Press has received honoraria for speaker’s bureau from Genentech. The preparation of this review was supported by Bristol-Myers Squibb and ImClone Systems Inc.

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  1. Department of Pathology, Keck School of Medicine, Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA

    Michael F. Press

  2. Division of Medical Oncology, Keck School of Medicine, FACP; University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Room 3456, Los Angeles, California, 90033, USA

    Heinz-Josef Lenz

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Press, M.F., Lenz, HJ. EGFR, HER2 and VEGF Pathways. Drugs 67, 2045–2075 (2007). https://doi.org/10.2165/00003495-200767140-00006

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