Possible Interaction: Tretinoin and Gefitinib

“In addition, it remains unclear which cellular kinases are being targeted by gefitinib to elicit enhancement of ATRA action, although their elucidation may provide novel targets for therapeutic intervention in AML.”

“Similarly, the combination of ATRA and gefitinib resulted in enhanced induction of U937 cell differentiation, as assessed by CD11b expression analysis (Figure 2b).”

“Strikingly, enhancement of ATRA-induced differentiation was observed even when gefitinib was added as late as 24 h after initiation of ATRA treatment (data not shown), suggesting that inhibition of later or prolonged kinase signaling is important.”

“The combination of ATRA and gefitinib , however, yielded 41.7% CD11b positivity.”

“In vivo, the combination of gefitinib and ATRA prolonged survival compared to gefitinib- or vehicle-treated leukemic mice in a syngeneic transplantation model, while the gain in survival did not reach statistical difference compared to treatment with ATRA alone.”

“Moreover, the combination of gefitinib with ATRA and ATO promoted myeloid cell differentiation in ATRA- and ATO-resistant APL cells.”

“Our results suggest that gefitinib is a potential adjuvant agent that can mitigate ATRA and ATO resistance in APL cells.”