Lung Cancer Therapeutic Program
We have used miRNA expression analyses in lung tumors and miRNA functional studies in lung cancer cell lines to identify miRNAs with therapeutic potential. The focus of our studies are miRNAs that consistently show lost or reduced expression levels in lung cancer samples and – when introduced into lung cancer cells – affect cell proliferation, viability, apoptosis, and/or cell cycle. These miRNAs are being tested in animal models for their capacity to reduce or eliminate tumor growth either when used alone or in combination with chemo- or radiation therapy.
Lung cancer is the leading cause of death among the various cancers, with more than 400,000 people succumbing to the disease each year (over 160,000 in the U.S. alone). More than 450,000 new cases of lung cancer are diagnosed each year. The lung cancer therapeutics market in the United States currently has an estimated value of $1.6 billion and the total annual cost of the disease exceeds $10 billion.
Human lung cancer is not a single disease but can be divided into several histologically identifiable subtypes. The two major groups of lung cancer types are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC develops from the transformation of pulmonary neuroendocrine cells and accounts for about 20% of all lung cancer. NSCLC originates from other epithelial cell types and usually metastasizes more slowly than SCLC. NSCLS is subdivided into squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. The subtyping of NSCLC depends on the tumor histology and where in the airways the transforming event has occurred.
Survival of lung cancer patients is strongly related to the stage of disease. The cure rate after surgical resection in patients without distant or loco-regional tumor spread is > 70%. Unfortunately, 85% of the patients have advanced disease stage at presentation, precluding treatment with curative intent. Attempts to improve the dismal outcome of advanced stage cases by therapeutic interventions such as chemo- and radiotherapy have extended the lives of lung cancer patients but have proven incapable of curing the disease. Multiple targeted therapies have entered clinical trials; however, only Iressa (gefitinib) and Tarceva (erlotinib) have shown sufficient patient benefit to receive FDA approval. Iressa and Tarceva are tyrosine kinase inhibitors that extend the lives of lung cancer patients with altered EGFR activity by several months.