BC Cancer Agency
Vancouver, British Columbia
Therapeutic targeting of the miR-106a-363 cluster in acute myeloid leukemia
Despite improved therapies, the 5-year relative survival for acute myeloid leukemia (AML) is currently 21% in Canada, with especially unfavorable prognosis for elderly patients. Therefore, new treatments that target the root of AML, leukemic stem cells (LSCs), are necessary. The current standard of care in elderly patients with AML, a combination of Venetoclax and azacytidine, has significantly improved overall survival. However, one third of responders relapsed, suggesting incomplete eradication of LSCs and thus making further investigation critical. MicroRNAs (miRNAs) exert key functions in LSCs and their dysregulation affects prognosis and outcome in AML patients. Furthermore, modulation of miRNA levels has shown promising results in preclinical models. Here we explore targeting LSCs through inhibition of a cancer-causing microRNA cluster in combination with Venetoclax and azacytidine. The proposed combination potentially intensifies depletion of LSCs and therefore has clinical potential not only in AML but also in other cancers such as lymphomas, multiple myeloma and solid tumors.