Research ArticleCancer

Inhibition of mitochondrial translation overcomes venetoclax resistance in AML through activation of the integrated stress response

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Science Translational Medicine  30 Oct 2019:
Vol. 11, Issue 516, eaax2863
DOI: 10.1126/scitranslmed.aax2863

Triple threat for leukemia

Acute myeloid leukemia is a relatively common and aggressive cancer with few good therapeutic options thus far. Venetoclax, a drug that promotes apoptosis, has shown some promise in this disease, but it has been limited by the development of resistance. Using a high-throughput screen, Sharon et al. determined that ribosome-targeting antibiotics such as tedizolid can help overcome venetoclax resistance by suppressing mitochondrial respiration and activating the cellular stress response. The combination was even more effective with the addition of the epigenetic drug azacitidine, both in vitro and in mouse models of leukemia, suggesting the translational potential of these treatments.

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