Research ArticleCancer

Overcoming adaptive therapy resistance in AML by targeting immune response pathways

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Science Translational Medicine  04 Sep 2019:
Vol. 11, Issue 508, eaaw8828
DOI: 10.1126/scitranslmed.aaw8828

Killing two pathways with one inhibitor

Acute myeloid leukemia is an aggressive cancer that can be difficult to treat because of rapidly evolving therapeutic resistance. Melgar et al. focused on a subtype of acute myeloid leukemia characterized by mutations in a gene called FLT3. Although FLT3 inhibitors can target oncogenic signaling pathways in this cancer, their effects do not last. The authors identified a pathway involved in the innate immune stress response, whose activation promoted resistance to drugs targeting the FLT3 pathway, and then developed an inhibitor that targets both pathways at once. This multikinase inhibitor showed promising results in vitro and in animals, suggesting its potential for clinical translation.

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