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Annals of Oncology Advance Access originally published online on April 3, 2008
Annals of Oncology 2008 19(7):1219-1223; doi:10.1093/annonc/mdn048
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

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Src as a potential therapeutic target in non-small-cell lung cancer

G. Giaccone1,* and P. A. Zucali2

1 Center for Cancer Research, National Cancer Institute, Bethesda, USA
2 Dipartimento di Oncologia ed Ematologia, Istituto Clinico Humanitas, Rozzano, Italy

* Correspondence to: Dr G. Giaccone, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Building 10, Room 12N226, Bethesda MD 20892-1906, USA. Tel: +1 301 4023415; Fax: +1 301 4020172; E-mail: giacconeg{at}mail.nih.gov

Lung cancer is the most common cause of cancer-related death, with non-small-cell lung cancer (NSCLC) accounting for 80%–85% of all cases. Although survival rates are reasonably good for patients diagnosed with very early disease, the majority of patients present with advanced disease. For these patients, palliation and improvements in quality of life are the primary goals of therapy. Although chemotherapeutic agents remain the cornerstone of first-line therapy, these agents have limited use in patients who have relapsed and have metastatic disease. Therefore, new strategies are required to improve survival and quality of life in this setting. With the substantial advances in our understanding of tumour biology, it has been possible to identify signalling pathways involved in mediating tumour growth and progression. These pathways offer targets for new biological agents such as small molecule inhibitors and monoclonal antibodies. One such target is Src, a tyrosine kinase that is involved in multiple aspects of tumorigenesis including proliferation, migration and angiogenesis. Increased levels of Src expression have been found in a range of cancers, especially breast, colorectal, prostate and lung. Preliminary preclinical data and pharmacodynamic data suggest that Src inhibition is a viable therapeutic option in the treatment of advanced NSCLC.

Key words: non-small cell lung cancer, Src, targeted therapy, tyrosine kinase

Received for publication October 15, 2007. Revision received January 29, 2008. Accepted for publication February 1, 2008.


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