Medical Department, Division of Oncology, ASST di Cremona, Ospedale di Cremona, Cremona, Italy.
Centre for Molecular Pathology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
Target Oncol. 2018 Aug;13(4):423-436. doi: 10.1007/s11523-018-0580-3.
Receptor tyrosine kinases (RTKs) are widely expressed transmembrane proteins that act as receptors for growth factors and other extracellular signalling molecules. Upon ligand binding, RTKs activate intracellular signalling cascades, and as such are involved in a broad variety of cellular functions including differentiation, proliferation, migration, invasion, angiogenesis, and survival under physiological as well as pathological conditions. Aberrant RTK activation can lead to benign proliferative conditions as well as to various forms of cancer. Indeed, more than 70% of the known oncogene and proto-oncogene transcripts involved in cancer code for RTKs. Consequently, these receptors are broadly studied as targets in the treatment of different tumours, and a large variety of small-molecule tyrosine kinase inhibitors (TKIs) are approved for therapy. In most cases, patients develop resistance to the TKIs within a short time. MicroRNAs are short (18-22 nucleotides) non-protein-coding RNAs that fine-tune cell homeostasis by controlling gene expression at the post-transcriptional level. Deregulation of microRNAs is common in many cancers, and increasing evidence exists for an important role of microRNAs in the development of resistance to therapies, including TKIs. In this review we focus on the role of microRNAs in mediating resistance to small-molecule TKIs in solid tumours.
受体酪氨酸激酶（RTKs）是广泛表达的跨膜蛋白，作为生长因子和其他细胞外信号分子的受体。配体结合后，RTKs 激活细胞内信号级联反应，因此参与多种细胞功能，包括分化、增殖、迁移、侵袭、血管生成和在生理及病理条件下的存活。异常的 RTK 激活可导致良性增殖性疾病以及各种形式的癌症。事实上，已知的 70%以上与癌症相关的癌基因和原癌基因转录本编码 RTKs。因此，这些受体被广泛研究作为治疗不同肿瘤的靶点，并且批准了多种小分子酪氨酸激酶抑制剂（TKI）用于治疗。在大多数情况下，患者在短时间内对 TKI 产生耐药性。microRNAs 是短的（18-22 个核苷酸）非编码蛋白 RNA，通过在转录后水平控制基因表达来微调细胞内稳态。microRNAs 的失调在许多癌症中很常见，越来越多的证据表明 microRNAs 在治疗耐药性的发展中起着重要作用，包括 TKI。在这篇综述中，我们重点关注 microRNAs 在介导实体瘤中小分子 TKI 耐药性中的作用。
