Across both sexes lung cancers are the most frequently diagnosed neoplasms. Furthermore, of all cancers, lung cancers have one of the poorest 5-year survival rates and consequently, between 1970 and 1994, lung cancers claimed the lives of almost 2.5million white Americans. This data is mirrored across most races and most geographical regions and consequently more effective treatments of lung cancers are required. In the latter part of the 20th century much hope was pinned on the use of antibody therapies in the treatment of cancer however for a number of reasons many exciting leads failed to generate clinical treatments and consequently the therapeutic use of antibodies now largely focuses on their ability to target toxins or isotopes to tumors (click here to access our recent dossier "Targeted immunotherapy of cancer" for more information). One notable exception to this trend is Trastuzumab, a humanized monoclonal antibody that binds to human epidermal growth factor-2 (HER2). Trastuzumab was originally launched in the US in 1999 for the treatment of advanced breast cancers that overexpress HER2/neu protein. Trastuzumab is able to prevent DNA repair thus improving the toxicity of chemotherapies, reduce the expression of HER2 on the cell surface leading to reduced responsiveness to growth factors and, initiate antibody-dependent cell-mediated cytotoxicity. Herceptin has thus been shown to increase the 1 year survival rates and time to disease progression in patients being treated with paclitaxel or anthracyclines/cyclophosphamide, and furthermore treatment is also effective when administered as a montherapy. HER2 protein is overexpressed in 20% to 66% of resected non-small cell lung cancer (NSCLC) tumors, and has been shown to predict poor patient outcome suggesting that Trastuzumab should be effective in this sub-group of lung cancer patients. Preclinical studies with NSCLC cell lines show that HER2 overexpression increases chemoresistance, invasiveness, and metastatic potential of the cells. In mouse xenograft experiments, Trastuzumab halts tumor growth and is synergistic with cytotoxic chemotherapy. Ongoing phase II trials are showing that trastuzumab can be added to standard chemotherapy in the treatment of patients with advanced NSCLC without additional toxicity and with promising efficacy. Whether trastuzumab will show a clear benefit for patients with NSCLC, either alone or in combination with established chemotherapy, remains to be proven in phase III testing.

Adapted from Azzoli et al, Semin Oncol 2002 Feb;29(1 Suppl 4):59-65

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