Repurposing ribosome-targeting antibiotics to overcome resistance to venetoclax in acute myeloid leukemia

David Sharon; Steven M Chan

doi:10.1080/23723556.2020.1712182

Repurposing ribosome-targeting antibiotics to overcome resistance to venetoclax in acute myeloid leukemia

Mol Cell Oncol. 2020 Jan 28;7(2):1712182. doi: 10.1080/23723556.2020.1712182. eCollection 2020.

Authors

David Sharon¹, Steven M Chan¹

Affiliation

¹ Department of Hematology and Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Abstract

Venetoclax, a selective B-cell lymphoma 2 inhibitor, has shown promise in the treatment of acute myeloid leukemia. However, the development of drug resistance limits its clinical efficacy. In our study, we discovered that ribosome-targeting antibiotics can be repurposed to overcome venetoclax resistance in AML cells through activation of the integrated stress response.

Keywords: Acute myeloid leukemia; BCL-2 inhibitor; antibiotics; drug resistance; integrated stress response; mitochondrial translation.

Grants and funding

This project was supported by the UpCycle Drug Repurposing Grant from the Cancer Research Society, an Operating Grant from the Leukemia and Lymphoma Society of Canada, and a Project Grant from the Canadian Institutes of Health Research (PJT-159521).