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撰文 | 黄宇翔
责编 | 黄俊如
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在小鼠肿瘤模型中,激活10%癌细胞的焦亡通路就可以显著抑制肿瘤的生长。[16]
如果我们把肿瘤组织想象成一座坚固的“堡垒”,其周围有肿瘤微环境筑成的 “护城河” 保护,使得免疫细胞向其发出的每一次进攻都无功而返。而小剂量的焦亡通路激活剂就像是一个个“炸药包”,能在肿瘤城堡的墙角下炸出一些缺口,进而辅助我们自身的免疫细胞攻破肿瘤细胞的城池。
GSDM具有成为小分子药物靶点潜力的依据:一些关键位点的突变可以导致GSDM家族蛋白处于持续激活状态。[6]
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[9] Heusel, J. W., Wesselschmidt, R. L., Shresta, S., Russell, J. H. & Ley, T. J. Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells. Cell 76, 977-987 (1994).
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[15] Zhang, Z. et al. Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature 579, 415-420 (2020).
[16] Wang, Q. et al. A bioorthogonal system reveals antitumour immune function of pyroptosis. Nature 579, 421-426 (2020).
制版编辑 | 皮皮鱼
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