SHP2 Inhibition with TNO155 Increases Efficacy and Overcomes Resistance of ALK Inhibitors in Neuroblastoma
使用 TNO155 抑制 SHP2 可提高神经母细胞瘤的疗效并克服 ALK 抑制剂的耐药性
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作者：Ivette Valencia-Sama, Lynn Kee, Gabriella Christopher, Michael Ohh, Mehdi Layeghifard, Adam Shlien, Madeline N Hayes, Meredith S Irwin
Significance
These findings highlight the translatability between zebrafish and murine models, provide evidence of aberrant RAS-MAPK signaling as an adaptive mechanism of resistance to lorlatinib, and demonstrate the clinical potential for SHP2/ALK inhibitor combinations for the treatment of ALK-mutant neuroblastoma, including those with acquired tolerance or potentially resistance to ALK-TKIs.
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