Professor, Pediatrics and Biochemistry
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey
Dr. Levine is working on two BCRF research studies that are focused on the role of tumor suppressor protein his laboratory discovered in 1979 called p53, which is mutated in about 60% of all human cancers. One study is focused on how p53 regulates cancer stem cells. Tumors are made up of different types of cells. Cancer stem cells are believed to be the origination cells from which the tumor arises and required for its growth and spread. Tumors that contain a lot of cancer stem cells are more aggressive and more likely to spread to distant tissues. Dr. Levine’s group has shown that breast cancer stem cells are more prevalent in tumors that lack a protein called p53, suggesting that p53 may be important in preventing their development. Dr. Levine and his team have identified additional proteins that may cause p53 to be turned off and thus promote stem cell generation in the tumor. They believe that by blocking these proteins, they may be able to prevent the stem cell production and tumor progression. They are currently working on ways to do this in the laboratory that will lead to new therapeutic agents for aggressive breast cancers.
When a cell is damaged beyond its ability to repair the damage, p53 activates processes that forcethe cell to die. When the p53 protein is mutated, as in cancers, it no longer functions properly, allowing damaged cancer cells to continue to grow and multiply. Working with his colleague, Dr. Darren Carpizo Dr. Levine identified a drug that can restore the normal function to mutant p53 protein and kill cancer cells. The research team is presently testing the drug in laboratory models of breast cancer with BCRA1 and p53 mutations with the goal of optimizing the drug or a related compound for clinical use in human breast cancer.
Arnold Levine has been a molecular biologist for the past 40 years, concentrating on cancer research. His lab discovered the p53 tumor suppressor and found its negative regulator, MDM2. He has published more than 200 papers in this area of research, and his lab has trained a very large number of scientists who continue to work in this field. Based upon this body of work, Dr. Levine has received nine honorary degrees and more than fifteen awards. In the past ten years, his laboratory has been at the forefront of work identifying and validating genetic variations in the p53 pathway that correlate with risk of cancer, age of onset and prognosis in breast cancers. They discovered and elucidated a naturally occurring single nucleotide polymorphism (SNP 309) in the promoter region of the MDM2 gene and demonstrated that the genotype at a specific locus can affect how hormones like estrogen affect tumorigenesis in humans. They continue to carry out novel research in this area.