Novel Approaches to Lung Cancer Research
Initial Award Abstract
Lung cancer is the most common cause of cancer-related death in the United States, and the high mortality reflects the invasive nature of the disease and its resistance to all current treatment modalities. Efforts to develop effective lung cancer prevention and treatment strategies have stimulated a strong interest in understanding the biology of lung neoplasia. Scientists now appreciate that the tumor microenvironment plays a critical role in lung cancer development and the clinical responses to radiotherapy and chemotherapy. It is known that tumors frequently evolve under conditions of abnormally low oxygen and nutrient supplies due to limited blood flow. Importantly, these stressed tumor cells are frequently less responsive to all currently available cancer therapies. A pressing need therefore exists for improved model systems, which allow scientists to probe the inner workings of lung cancer cells, such as variations in the supplies of oxygen and nutrients needed for tumor growth, and to develop therapeutic strategies targeting this highly resistant group of tumor cells.
Our hypothesis is that development and application of three-dimensional culture systems of human lung cancer cells will mimic the metabolically stressful environment that tumor cells experience when growing within the lung tissue. In other words, we intend to develop novel 3-D culture systems of lung cancer cells as test-tube models of actual tumors. We will then utilize these tumor-like masses to explore the responses of energy-stressed cancer cells to known chemo- and radio-therapeutic agents, and, importantly, to identify novel targets and therapeutics for lung cancer treatment.
Currently, nearly all of the laboratory research performed with human lung cancer cells employs decades-old technologies involving cells cultured as single-cell layers on plastic dishes. We hope to be able to change this paradigm by demonstrating the relevance and utility of 3-D culture systems for detailed dissections of tumor biology, and to prove that these systems offer unparalleled opportunities for the development of novel agents for cancer therapy. Importantly, our research squarely focuses on the tumor cells that oncologists consider most resistant to conventional chemotherapy and radiotherapy – the metabolically stressed cell that resides in the interior of the lung tumor mass. If our studies prove to be successful, our findings may open completely new vistas in lung cancer research, and provide a considerable benefit in the therapy of lung cancer. |