Mark Fuster, M.D., assistant professor in the Division of Pulmonary and Critical Care Medicine in UCSD’s Department of Medicine, is passionate about attacking the mechanism of lung cancer invasion and metastasis at the cellular level. A grant from Joan’s Legacy: The Joan Scarangello Foundation to Conquer Lung Cancer, will help Dr. Fuster explore a novel multi-targeting strategy against a form of lung adenocarcinoma known as bronchoalveolar carcinoma. His research project “Novel Targeting for Two Faces of Bronchioalveolar Carcinoma” earned him one of 12 grants to fund lung cancer research that were distributed nationwide by the private foundation in December 2007.
Lung cancer is the number one cancer killer in the United States, taking more than 160,000 lives each year. Bronchioalveolar carcinoma (or BAC) makes up about 3-4% of lung cancers. BAC is not as strongly associated with smoking as the more common forms of lung cancer, according to Fuster, who added that about 10-15% of all lung cancers are non-smoking related.
“In its pure form, this cancer develops like sheets instead of a typical mass or tumor,” he said. “Such tumors tend to spread more rapidly through air sacs and the airways, much like pneumonia is able to spread in the lung.” At the same time, Fuster noticed that an increasing amount of research as well as clinical practice in pathology has revealed a novel twist, or “second face” to this cancer. Pathologists report that a substantial portion of adenocarcinomas (tumors that make up over one-third of all lung cancer cases) harbor regions within them that are made up of BAC-type cells. In such cases, invasion and metastasis of the cancer cells may depend on the growth of blood vessels into the tumors, rather than spreading through the airways, according to Fuster.
“Compared to other forms of lung cancer, BAC tumors tend to have better responses to a form of chemotherapy that targets a growth receptor known as the Epidermal Growth Factor Receptor or EGFR,” said Fuster. “Other lines of research have revealed that growth of BAC depends on other growth factor pathways – pathways that may rely on the action of complex carbohydrate molecules known as proteoglycans. Together with collaborators including Dr. Jeffrey Esko, Professor of Cellular & Molecular Medicine at UCSD, we have some experience targeting such molecules.”
Fuster plans to research the effects of combining EGFR antagonists, such as the drug erlotinib, with novel ways to block the action of proteoglycans on both BAC cells as well as blood-vascular (or endothelial) cells.
Fuster will look at whether these two therapies are synergistic in targeting both faces of BAC – the pure form and the form that may lurk in a larger portion of lung cancers.
Dr. Fuster also has funding from the American Cancer Society as well as the U.S. Department of Veterans Affairs to study the molecular mechanisms by which lymphatic vasculature contributes to lymph node metastasis in lung cancer.