TY - JOUR
T1 - FLT3 Inhibitors
T2 - A paradigm for the development of targeted therapeutics for paediatric cancer
AU - Brown, P.
AU - Small, D.
N1 - Funding Information:
This work was supported by grants from the National Cancer Institute (NCI) (T32CA60441 to P.B., CA91177 and CA90668 to D.S.), Leukemia and Lymphoma Society (to D.S.), and Children's Cancer Foundation (to D.S.). D.S. is the Douglas Kroll Research Foundation Translational Researcher of the Leukemia and Lymphoma Society. Note added in Proof
PY - 2004/3
Y1 - 2004/3
N2 - The area of molecularly-targeted cancer therapeutics is generating tremendous interest and excitement. While clinical investigation of these agents has been largely limited to adults, clinical trials for paediatric cancer patients with many of these agents are now underway. This paper reviews the current status of molecularly-targeted therapies for paediatric malignancies, with special attention given to one class of agents, inhibitors of the FLT3 receptor tyrosine kinase. FLT3 is expressed and activated in many human leukemias, including a significant percentage of pediatric AML and infant and childhood ALL, especially in the setting of MLL gene rearrangement. Activating mutations of FLT3 portend a poor prognosis in pediatric AML. Activated FLT3 can be effectively and selectively targeted by small molecule inhibitors, and these agents have shown promise in early phase clinical trials in adults with AML. Limited preclinical data with FLT3 inhibitors in MLL-rearranged ALL have also been reported. Challenges and future directions for the use of FLT3 inhibitors and other targeted agents in paediatric cancer are discussed.
AB - The area of molecularly-targeted cancer therapeutics is generating tremendous interest and excitement. While clinical investigation of these agents has been largely limited to adults, clinical trials for paediatric cancer patients with many of these agents are now underway. This paper reviews the current status of molecularly-targeted therapies for paediatric malignancies, with special attention given to one class of agents, inhibitors of the FLT3 receptor tyrosine kinase. FLT3 is expressed and activated in many human leukemias, including a significant percentage of pediatric AML and infant and childhood ALL, especially in the setting of MLL gene rearrangement. Activating mutations of FLT3 portend a poor prognosis in pediatric AML. Activated FLT3 can be effectively and selectively targeted by small molecule inhibitors, and these agents have shown promise in early phase clinical trials in adults with AML. Limited preclinical data with FLT3 inhibitors in MLL-rearranged ALL have also been reported. Challenges and future directions for the use of FLT3 inhibitors and other targeted agents in paediatric cancer are discussed.
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U2 - 10.1016/j.ejca.2003.08.030
DO - 10.1016/j.ejca.2003.08.030
M3 - Article
C2 - 15010072
AN - SCOPUS:1542269168
SN - 0959-8049
VL - 40
SP - 707
EP - 721
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 5
ER -