c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.

中文翻译：

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c-KIT 受体酪氨酸激酶在癌症中的作用和意义：综述。


c-kit 是一种经典的原癌基因，编码对干细胞因子 (SCF) 做出反应的受体酪氨酸激酶 (RTK)。 C-KIT 信号传导是细胞增殖、存活和迁移的关键调节因子，与多种生理过程有关，包括色素沉着、造血和肠道运动。越来越多的证据表明，由 c-kit 过度表达或突变引起的 c-KIT 功能失调可促进各种人类癌症的肿瘤发生和进展。在这篇综述中，我们讨论了 c-KIT 最重要的结构和生物学特征，以及对 SCF 与该 RTK 结合后细胞内信号通路激活的见解。然后，我们阐述了不同的 c-kit 改变如何与特定的人类癌症相关，并描述了最近的研究，这些研究强调了 c-KIT 在不同实验模型中对癌症干性、上皮间质转化和转移性疾病进展的贡献。总结了酪氨酸激酶抑制剂在治疗 c-KIT 阳性肿瘤中的影响以及由于其产生耐药性的倾向而产生的局限性。最后，我们评估了更有选择性地针对 c-KIT 的新型治疗方法的潜力，同时最大限度地减少对正常组织的毒性。