Focus
Dr. Sugarbaker’s research focuses on noncardiac thoracic disease, with particular emphasis on lung cancer and mesothelioma. “Lung cancer is the number one fatal cancer in the United States,” Dr. Sugarbaker states, “and the majority of patients present with inoperable stage IV disease. As a consequence, only about 20 percent of patients present early enough to be suitable surgical candidates.”
Mesothelioma is an extremely rare cancer of the pleural space (the two-layer membrane that lines the chest wall cavity and covers the lungs). It has long been associated with occupational exposure to asbestos. “We are in the midst of a worldwide epidemic of mesothelioma,” Dr. Sugarbaker advises, “both in the United States and in Europe, where the epidemic is not expected to peak until 2020.” The focus of Dr. Sugarbaker's work over the past several decades has been the development of innovative surgical techniques and basic research to deal with these devastating afflictions. Dr. Sugarbaker is particularly renowned for his work with mesothelioma. He is largely credited with developing the surgical technique for mesothelioma resection and for recognizing the importance of a multimodality approach to treatment that combines surgery with chemotherapy and radiation therapy. Founder and current director of the International Mesothelioma Program based at Brigham and Women’s Hospital, Dr. Sugarbaker operates on mesothelioma patients from all parts of the world, and he and his colleagues are at the forefront of translational research to find a definitive cure.
Background
Dr. David Sugarbaker was raised in Missouri. The son of a surgeon, he was inspired from an early age to pursue a career in surgery and cancer research. He attended Wheaton College outside of Chicago, Illinois and then went on to Cornell University Medical College in New York City. Dr. Sugarbaker first came to the Peter Bent Brigham Hospital as an intern in 1982, spending two years of his general residency in research at the Harvard-Thorndyke Laboratory. After finishing his surgical residency in 1986 as Chief Resident, he went to the University of Toronto for two additional years of specialized training in thoracic surgery under the noted Dr. Griffith Pearson. In 1988, Dr. David J. Sugarbaker, M.D. Sugarbaker was invited back to the Brigham to be chief of the new Division of Thoracic Surgery, established by Dr. John Mannick (then chief of surgery). Dr. Sugarbaker is the Richard Wilson Professor of Oncologic Surgery at Harvard Medical School and Chief of the Division of Thoracic Surgery, as well as a co-leader of the Brigham Biomedical Research Institute’s Cancer Research Center.
Research
As he began to see a greater number of patients with mesothelioma for whom there really were no good treatment options, Dr. Sugarbaker was inspired to develop a surgical technique (extrapleural pneumonectomy) to remove this tumor, and subsequently refined it to its present practice, which has an extremely low operative mortality. The development of this procedure greatly increased the number of patients who came to the Brigham for surgical resection. This led to the genesis of the Thoracic Oncology Tumor Bank. From humble beginnings in a borrowed corner of a pathology department freezer, the effort to bank lung tumor tissue has grown into a sophisticated large laboratory housing more than 30,000 specimens. In recognition of the quality of this facility, the tissue bank has recently been designated as a National Genome Project Biorepository. In the early 1990’s Dr. Sugarbaker began to publish papers describing markers related to systemic recurrence of mesothelioma, leading to the thought that patients could be prophylactically treated with adjunct chemotherapy and radiation. In Dr. Sugarbaker's laboratory and the several laboratories under his direction, he and his colleagues have been examining gene ratios in thoracic cancers, which appear to improve the accuracy of tumor classification and prognostication. Originally established to examine genetic biomarkers, Dr. Sugarbaker’s laboratory has also moved in the direction of identifying protein markers in tumors, such as non-small cell lung cancer and mesothelioma, and this represents an additional focus of ongoing research.
Laboratory
Dr. Sugarbaker’s laboratory is staffed with approximately 12 postdoctoral fellows, technicians, database managers, and senior faculty.
Dr. Sugarbaker’s laboratories are funded through the National Cancer Institute, as well as the International Mesothelioma Program. Additionally, his laboratories and investigators receive other Federal and private support.
Collaborations
Advancement in lung cancer and mesothelioma research is dependent on input from multiple experts: epidemiologists, pathologists, oncologists, radiologists, radiation oncologists, geneticists, statisticians, and molecular biologists. Dr. Sugarbaker’s laboratory has benefited particularly from close proximity to the Harvard School of Public Health, which has resulted in many fruitful collaborations with experts in population studies, including a notable collaboration with Dr. Karl Kelsey. Dr. Kelsey is an expert in occupational exposure to asbestos and a basic scientist who has been working to elucidate the causes of mesothelioma. He and his associates are working with Dr. Sugarbaker and his staff to develop translational therapies based on a deeper knowledge of the clinical subtypes and gene expression patterns found in mesothelioma. Drs. Kelsey and Sugarbaker are currently collaborating to identify genetic susceptibility to mesothelioma and to investigate the role of epigenetic silencing using microarray technologies to identify gene expression profiles. In the area of lung cancer, they are examining the importance of mutations in the epidermal growth factor (EGF) receptor, which have been found in a population of nonsmoking women. Dr. Sugarbaker also benefits from a longstanding collaboration with Dr. John Godleski, an epidemiologist and expert in the physical properties of asbestos that render this material so highly carcinogenic.
Importance of Being at the Brigham
“The strength of the Brigham and Women’s Hospital, the Brigham Biomedical Research Institute, and the Cancer Research Center,” Dr. Sugarbaker explains, “is the outstanding faculty and clinical staff, the large patient population, and the dedicated research efforts of this large body of investigators, all of which are essential ingredients for great discovery and medical innovation, which is true to the history and tradition of the Brigham.”
Future
Dr. Sugarbaker looks forward to a time when the molecular and genetic expression of lung cancers and mesotheliomas have been fully developed, such that tailoring treatment plans to individual patients will be routine, leading to earlier screening and identification of disease and extended survival or cure.
Selected References
Gordon GJ, Jensen RV, Hsiao L, Gullans SR, Blumenstock JE, Ramaswamy S, Richards WG, Sugarbaker DJ, Bueno R. Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma. Cancer Res. 2002;62:4963-4967.
Gordon GJ, Jensen RV, Hsiao L, Gullans SR, Blumenstock JE, Richards WG, Jaklitsch MT, Sugarbaker DJ, Bueno R. Using gene expression ratios to predict outcome among patients with mesothelioma. J Natl Cancer Inst. 2003;95:598-605.
Gordon GJ, Richards WG, Sugarbaker DJ, Jaklitsch MT, Bueno R. A prognostic test for adenocarcinoma of the lung from gene expression profiling data. Cancer Epidemiology Biomarkers & Prevention. 2003;12: 905-910.
Gordon GJ, Rockwell GN, Jensen RV, Rheinwald JG, Glickman JN, Aronson JP, Pottorf BJ, Nitz MD, Richards WG, Sugarbaker DJ, Bueno R. Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using largescale transcriptional profiling. Am J Pathol. 2005;166:1827-1840.
Gordon GJ, Rockwell GN, Godfrey PA, Jensen RV, Glickman JN, Yeap BY, Richards WG, Sugarbaker DJ, Bueno R. Validation of genomics-based prognostic tests in malignant pleural Mesothelioma. Clin Cancer Res. 2005;11:4406-4414.