Exploiting macropinocytosis for drug delivery into KRAS mutant cancer.
Exploiting macropinocytosis for drug delivery into KRAS mutant cancer.
复制标题
利用巨噬细胞吞噬作用向KRAS突变癌症输送药物。
作者：
Liu H;Qian F
KRAS突变是与癌症相关的最常见的基因突变之一，约25%的肿瘤，尤其是胰腺癌、肺癌和结直肠癌。长期以来，突变型KRAS一直被认为是一种不可治疗的靶标，多年来一直阻碍着直接KRAS靶向的进展，而利用其转化的代谢行为将靶向药物递送到KRAS突变型细胞中可能会提供另一种机会。巨胞饮是一种非选择性的液相内吞途径，被发现在KRAS驱动的肿瘤中作为一种代谢特征被上调，并在从细胞外液获取营养中起关键作用。随着观察到多种药物递送系统可以通过巨胞饮作用被KRAS突变型癌细胞内化，利用巨胞饮作用将治疗剂细胞内递送到KRAS突变型肿瘤细胞中正在成为一种新的药物递送探索。在这篇文章中，我们总结了癌症生物学研究，检查KRAS突变诱导的巨胞饮，回顾了最近的研究，利用巨胞饮增强KRAS突变癌细胞选择性药物输送，并讨论了潜在的机会，挑战和陷阱，这一战略。
KRAS mutations are one of the most common gene mutations linked to cancer, presenting in approximately 25% of all tumors, especially pancreatic, lung, and colorectal cancers. Mutant KRAS has long been considered an undruggable target, stalling progress in direct KRAS targeting for many years, while targeted drug delivery into KRAS mutant cells utilizing their transformed metabolic behavior might present an alternative opportunity. Macropinocytosis, a nonselective, fluid-phase, endocytic route, was found to be upregulated as a metabolic feature in KRAS-driven tumors and plays a critical role in nutrient acquisition from extracellular fluids. With the observation that a variety of drug delivery systems could be internalized by KRAS mutant cancer cells through macropinocytosis, exploiting macropinocytosis for intracellular delivery of therapeutics into KRAS mutant tumor cells is emerging as a new drug delivery expedition. In this article, we summarized cancer biology studies that examined KRAS mutation-induced macropinocytosis, reviewed recent studies exploiting macropinocytosis enhancement for KRAS mutant cancer cell-selective drug delivery, and discussed the potential opportunities, challenges and pitfalls of this strategy.
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