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Association details:
| Biomarker: | FLT3 D835Y |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | sorafenib (Multi-tyrosine kinase inhibitor, pan-RAF inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia
Excerpt:
...observed prominent mutations at residues D835 and F691 in blast samples at sorafenib resistance. Deep sequencing revealed low-level mutations in resistance samples as well as the evolution of mutations during sorafenib treatment….Cells with single D835H/Y mutants were resistant to sorafenib (IC50, 81 and 210 nM) in comparison to cells with the ITD only (IC50, 1.1 nM) (Table 3).
DOI:
https://dx.doi.org/10.1158%2F1078-0432.CCR-13-1323
Source:
Title:
Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia
Excerpt:
The five substitutions that conferred a high degree of resistance to AC220 in vitro were cross-resistant to sorafenib in cell-based growth and biochemical assays (Supplementary Fig. 4). The degree of relative resistance to sorafenib associated with these mutants was generally similar to that observed with AC220.
DOI:
https://dx.doi.org/10.1038%2Fnature11016
Trial ID:
