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Association details:
| Biomarker: | FLT3 D835Y |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | sunitinib (c-KIT inhibitor, VEGFR inhibitor, PDGFR 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:
Sunitinib suppressed leukemic clones with D835H and F691L mutations, but not D835Y. Cells expressing sorafenib-resistant FLT3 mutations were sensitive to sunitinib in vitro.
DOI:
https://dx.doi.org/10.1158%2F1078-0432.CCR-13-1323
Source:
Title:
An Innovative Phase I Clinical Study Demonstrates Inhibition of FLT3 Phosphorylation by SU11248 in Acute Myeloid Leukemia Patients
Excerpt:
The incidence of FLT3-D835 (exon 20) mutations was 3.4% (1 of 29), observed in patient 1 (D835Y)....The D835 patient in this study (1) showed weak transient inhibition consistent with low plasma drug levels (Cmax, 15 ng/ml; data not shown). These data clearly demonstrate that a single dose of SU11248 results in inhibition of FLT3 phosphorylation in a dose-dependent manner in AML patients, with inhibition in all genotype.
DOI:
10.1038/sj.onc.1206543
Source:
Title:
SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo
Excerpt:
SU11248 inhibited phosphorylation of FLT3-ITD with an IC50 of less than 10 nM. Similarly, phosphorylation of activation loop mutants Asp835Tyr, Asp835Val, and Asp835His was inhibited by SU11248, with IC50 values of 30 to 300 nM (Figure 2)....SU11248 also inhibited phosphorylation of Asp835 point mutations, Asp835Val, Asp835His, and Asp835Tyr....We show that SU11248 (20 mg/kg/d) dramatically regresses FLT3-ITD tumors in the subcutaneous tumor xenograft model and prolongs survival in the bone marrow engraftment model.
DOI:
10.1182/blood-2002-07-2307
