Background
Dr. Brown's research is focused on developing new therapies for childhood leukemia. Leukemia (cancer of the blood-forming cells in the bone marrow) is the most common form of cancer in children. While great improvements have been made in the rates of cure for children with leukemia overall, certain types of childhood leukemia continue to have very low cure rates with the best known treatments, and new treatments are clearly needed for these children. Furthermore, the standard treatments for childhood leukemia (intensive chemotherapy and, in some cases, bone marrow transplantation) can cause significant, and not uncommonly debilitating, acute and late complications. New treatments that are just as effective against the leukemia, but less toxic to the patient, could vastly improve the outlook for this disease. Recent advances in cancer research have enabled the discovery of genetic changes (mutations) which cause certain types of cancer, and subsequently to drugs which can target these mutated genetic pathways. These targeted drugs have the potential to be more effective and less toxic than the standard treatments.
Dr. Brown's lab has found that a gene called FLT3 (which was initially discovered by Dr. Brown's mentor, Dr. Don Small) is particularly important in the types of childhood leukemia with low cure rates. Several FLT3-targeted drugs (inhibitors) are being developed. Since leukemia is not caused by a single mutation, but rather by several mutations occurring together in the same cells, combinations of drugs are needed. Dr. Brown's lab has identified promising combinations of standard chemotherapy drugs and FLT3 inhibitors that can work together to more effectively kill leukemia cells. Based on this work, Dr. Brown, a member of the Johns Hopkins Kimmel Cancer Center, is now leading the first clinical trials of a FLT3 inhibitor combined with chemotherapy in children with leukemia through the Children's Oncology Group international network. In conjunction with these clinical trials, Dr. Brown's lab is performing further experiments in the laboratory to help optimize dosing, to develop a test that can be used to predict which patients are most likely to benefit from the new drugs, and to determine how leukemia cells are able to survive despite treatment.
Hopefully, these efforts will result in significant improvements in the cure rates for these children.
Dr. Brown's lab continues to investigate other ways to improve the treatment of childhood leukemia by developing therapies that can overcome resistance to chemotherapy, and, unlike chemotherapy, are selectively targeted to the mutations that cause leukemia. The success of these efforts depends in large part on the amazing work being done by our colleagues and collaborators here at Hopkins and elsewhere, and by our post-doctoral fellows and technicians who have joined the lab and bring new ideas, energy and a willingness to do the hard work that makes such advances possible.
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