Journal
EXPERT REVIEW OF HEMATOLOGY
Volume 8, Issue 3, Pages 299-313Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1586/17474086.2015.1032935
Keywords
acute myeloid leukemia; cell cycle; clinical studies; CXCL12; hedgehog signaling; isocitrate dehydrogenase; mesenchymal stem cell
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Funding
- Norwegian Cancer Society
- Solveig and Ove Lundes Foundation
- Heels-Vest
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Human acute myeloid leukemia is a heterogeneous disease and the effect of therapeutic targeting of specific molecular mechanisms will probably vary between patient subsets. Cell cycle regulators are among the emerging targets (e.g., aurora and polo-like kinases, cyclin-dependent kinases). Inhibition of communication between acute myeloid leukemia and stromal cells is also considered; among the most promising of these strategies are inhibition of hedgehog-initiated, CXCR4-CXCL12 and Axl-Gas6 signaling. Finally, targeting of energy and protein metabolism is considered, the most promising strategy being inhibition of isocitrate dehydrogenase in patients with IDH mutations. Thus, several strategies are now considered, and a major common challenge for all of them is to clarify how they should be combined with each other or with conventional chemotherapy, and whether their use should be limited to certain subsets of patients.
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