Abstract
Although pediatric leukemias and lymphomas currently have reasonably high cure rates, persistent cases of relapsed and refractory disease are still observed. Additionally, as a consequence of the chemotherapy and radiotherapy that produce the high cure rates, children commonly experience undesirable toxicities including end organ damage, infertility, and secondary malignancies. Therefore, the work of several researchers and clinicians continues to concentrate on identifying specific molecular targets that can be inhibited to provide effective therapy while avoiding detrimental side-effects. A key signaling pathway commonly dysregulated in pediatric leukemias and lymphomas is the phospho-inositol-3-kinase (PI3K)-AKT pathway. PI3K activity is increased due to somatic mutations PI3K regulatory or catalytic subunit genes, to increased protein expression of PI3K catalytic subunits, or to excess signaling from upstream oncogenic proteins. In parallel with clarification of the roles of various PI3K regulatory and catalytic subunits in pediatric disease, pharmaceutical companies have developed highly potent and specific inhibitors for the various PI3K catalytic subunits. This review will highlight the studies that have defined the role of the various PI3K regulatory and catalytic subunits in childhood hematologic malignancies, and address how these findings are now being translated in murine pre-clinical and human clinical trials.
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Acknowledgements
This work was supported by and the U.S. National Institutes of Health (HL104867, CBG; CA134777, RJC), the Riley Children’s Foundation, and the IUPUI Office of the Vice Chancellor for Research. The authors gratefully acknowledge the administrative assistance of Marilyn L. Wales.
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Goodwin, C.B., Chan, R.J. (2016). Phospho-Inositol-3-Kinase Activity and Dysregulation in Pediatric Leukemia and Lymphoma. In: Dey, N., De, P., Leyland-Jones, B. (eds) PI3K-mTOR in Cancer and Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-34211-5_7
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