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dasatinib + tretinoin
- Development stage
- Phase 1
- Lead developer
- Bristol Myers Squibb
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Dasatinib + tretinoin (all-trans retinoic acid, ATRA) is an experimental combination therapy investigated by the University of Pittsburgh for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The regimen combines dasatinib, a multi-targeted tyrosine kinase inhibitor that targets BCR-ABL and Src family kinases (SFKs), with tretinoin, a retinoid that induces cellular differentiation. The biological rationale for this combination is based on findings that SFKs are often hyperactivated in AML and can inhibit the retinoic acid receptor (RAR) signaling pathway, contributing to differentiation arrest. By inhibiting SFKs, dasatinib is thought to sensitize AML blasts to the differentiating effects of ATRA, potentially overcoming resistance in non-APL (acute promyelocytic leukemia) subtypes of AML. A Phase 1 study conducted at the UPMC Hillman Cancer Center evaluated this combination in elderly or relapsed/refractory patients, demonstrating safety but limited clinical efficacy.
- Other names
- ATRAall-trans retinoic acidtretinoindasatinib + all-trans retinoic acid
02
Targets
ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)EPHA2 (Ephrin type-A receptor 2)PDGFRB (Platelet-derived growth factor receptor beta)RARA (Retinoic acid receptor alpha)KIT (c-KIT proto-oncogene receptor tyrosine kinase)SRC (Proto-oncogene tyrosine-protein kinase Src)
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