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Association details:
| Biomarker: | MCL1 overexpression |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Venclexta (venetoclax) (Bcl2 inhibitor) + tamnorzatinib (ONO-7475) (AXL inhibitor, MERTK inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
AXL/Mertk Inhibitor ONO-7475 Potently Synergizes with BCL2 Inhibitor ABT-199, Overcomes ABT-199 Resistance Mechanisms, and Kills FLT3 ITD AML Cells
Published date:
11/06/2019
Excerpt:
FLT3-ITD AML cell lines Molm13 and MV4;11 as well as ABT-199 resistant MV4;11 cells and MV4;11 cells that overexpress MCL-1 or gain-of-function (GOF) MCL-1 mutant S159A were treated with varying doses of ONO-7475 in the presence and absence of ABT-199….ONO-7475/ABT-199 combination was superior to either single agent in reducing leukemia burden as determined by IVIS imaging and examination of BM, spleen and liver. Critically, the combination of these two agents had a synergistic effect and significantly increased survival compared to either ABT-199 or ONO-7475 alone.
DOI:
https://doi.org/10.1182/blood-2019-128626
