Research: Laboratory Program –
Jack D. Burton, M.D.

Dr. Burton is currently an Assistant Member at GSCC and is also Director of Oncology Research at Staten Island University Hospital. He received his M.D. degree from the University of Minnesota in 1981, and went on to complete his residency training at this institution. He completed a fellowship in hematology/oncology at the same institution and did basic laboratory studies during this time under Dr. Neil Kay addressing chronic lymphocytic leukemia. This common leukemia served as a model for exploring cancer-related abnormalities of the immune system that are also observed in many other cancer types. After completing fellowship training, he joined the laboratory of Dr. Thomas Waldmann at the National Cancer Institute, where he performed studies addressing novel molecules that are involved in key functions of the immune system.

After joining the Center, Dr. Burton continued his work in immunology and developed strategies for the use of specific immune-system proteins known as cytokines for the treatment of several important cancers. Dr. Burton has actively participated in the Center's clinical program to develop and carry out clinical trials utilizing radiolabeled anti-tumor antibodies to treat both lymphomas and solid tumors. In his laboratory, he has been testing the potential of antibodies directed against another tumor target, known as MUC1, for the treatment of multiple myeloma and an array of solid tumors. His laboratory has identified ways to selectively increase levels of this target antigen in order to increase the efficacy of this specific antibody-based approach to cancer treatment.

He has also explored approaches to improve the efficacy of cancer treatment using clinically available drugs such as COX-2 inhibitors (e.g., Celebrex®) and "TZDs" (anti-diabetic drugs), which themselves have anti-cancer effects. These drugs are examples of newer, targeted treatments for cancer that specifically bind to proteins in cancer cells that promote their growth. Thus, they tend to be better tolerated than conventional treatment modalities, and they can safely be added to these other modalities. Along with colleagues at Staten Island University Hospital, Dr. Burton has applied these findings to clinical trials in both lung and primary brain cancers. The results to date show that the combination of Celebrex® with standard chemotherapy is well tolerated, indicating that such drugs can be added to other cancer treatments to improve overall anti-tumor activity.

Dr. Burton has also been involved in studies that address the timing of administration of anti-cancer biologics and drugs. These studies have shown that treatment at certain times of the day can significantly lower side effects and improve efficacy of cancer treatment in laboratory model systems. Better understanding of these circadian rhythms holds promise for improving cancer treatments.

1. Burton J, Goldman CK, Rao P, Moos M and Waldmann TA. Association of intercellular adhesion molecule-1 with the multichain high-affinity interleukin-2 receptor. Proc Natl Acad Sci, USA 87: 7329-7333 (1990).
2. Burton JD, Bamford RN, Peters C, Grant AJ, Kurys G, Goldman CK, Brennan J, Roessler E, and Waldmann TA. A lymphokine, provisionally designated interleukin-T, produced by a human adult T-cell leukemia line stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci, USA 91: 4935-4939 (1994).
3. Burton JD, Lew K, Mishina D, Cardillo T and Gold DV. Epithelial mucin-1 (MUC1) expression and MA5 anti-MUC1 monoclonal antibody targeting in multiple myeloma. Clin Cancer Res 5: 3065s-3072s (1999).
4. Blumenthal RD, Waskewich C, Goldenberg DM, Lew W, Flefleh C and Burton JD. Chronotherapy and chronotoxicity of the cyclooxygenase-2 inhibitor, celecoxib, in athymic mice bearing human breast cancer xenografts. Clin Cancer Res 7: 3178-3185 (2001).
5. Waskewich C, Blumenthal RD, Li H, Stein R, Goldenberg DM and Burton J. Celecoxib exhibits the greatest potency amongst COX-inhibitors for growth inhibition of COX-2-negative hematopoietic and epithelial cell lines. Cancer Res 62: 2029-2033 (2002).