Clinical center of Vojvodina, Medical faculty Novi Sad, University of Novi Sad, Hajduk Veljkova 1, 21000 Novi Sad, Serbia.
Curr Pharm Des. 2014;20(17):2849-80. doi: 10.2174/13816128113199990593.
Tumor progression is strongly associated with the activity of receptor tyrosine kinases (RTKs) and their intracellular signal transduction pathways, which regulate several cell functions including proliferation, apoptosis, motility, adhesion and angiogenesis. Detailed structural and functional studies of RTKs, including the stem cell factor receptor c-KIT, revealed the complexity of these receptor systems and contributed to development of targeted clinical approaches with relevance in both prognosis and therapy. C-KIT signaling network has been the subject of intense research and pharmaceutical strategies to identify novel target-based approaches for cancer treatment. Evidence that c-KIT signaling promotes cell proliferation and survival, along with the frequency in which this pathway is aberrantly activated in cancer, support the current efforts to identify approaches for its efficient inhibition. C-KIT mutations are associatied with several human malignancies, such as gastrointestinal stromal tumors, acute myeloid leukemia, mast cell leukemia, and melanoma. Novel therapies are developed that target some of the identified genetic defects. It is therefore anticipated that newly-identified genetic markers will acquire a predictive value, that is, the ability to predict differential efficacy of a therapy. This review describes the evolving understanding of c-KIT/SCF axis and their downstream signaling in cancer, and the strategies for c-KIT-directed targeted cancer therapy.
肿瘤的进展与受体酪氨酸激酶（RTKs）及其细胞内信号转导途径的活性密切相关，这些途径调节包括增殖、凋亡、运动性、黏附性和血管生成在内的多种细胞功能。对 RTKs（包括干细胞因子受体 c-KIT）的详细结构和功能研究揭示了这些受体系统的复杂性，并有助于开发具有预后和治疗相关性的靶向临床方法。c-KIT 信号网络一直是深入研究和药物研发的主题，旨在确定针对癌症治疗的新型基于靶标的方法。c-KIT 信号促进细胞增殖和存活的证据，以及该途径在癌症中异常激活的频率，支持目前努力寻找有效的抑制方法。c-KIT 突变与多种人类恶性肿瘤相关，如胃肠道间质瘤、急性髓性白血病、肥大细胞白血病和黑色素瘤。已经开发出针对一些已确定遗传缺陷的新型疗法。因此，可以预期新确定的遗传标志物将获得预测价值，即预测治疗效果差异的能力。本文综述了 c-KIT/SCF 轴及其在癌症中的下游信号转导的不断发展的认识，以及针对 c-KIT 的靶向癌症治疗策略。
