Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues and can thereby rapidly and reversibly alter the function of their protein substrates in the form of significant changes in protein confirmation and affinity for their interaction with protein partners to drive cellular functions under normal and pathological conditions. PTKs are classified into two groups: one of which represents tyrosine kinases, while the other one includes the members of the serine/threonine kinases. The group of tyrosine kinases is subdivided into subgroups: one of them includes the member of receptor tyrosine kinases (RTKs), while the other subgroup includes the member of non-receptor tyrosine kinases (NRTKs). Both these kinase groups function as an “on” or "off" switch in many cellular functions. NRTKs are enzymes which are overexpressed and activated in many cancer types and regulate variable cellular functions in response to extracellular signaling-dependent mechanisms. NRTK-mediated different cellular functions are regulated by kinase-dependent and kinase-independent mechanisms either in the cytoplasm or in the nucleus. Thus, targeting NRTKs is of great interest to improve the treatment strategy of different tumor types. This review deals with the structure and mechanistic role of NRTKs in tumor progression and resistance and their importance as therapeutic targets in tumor therapy.
蛋白酪氨酸激酶（PTKs）不仅是多种人类疾病（包括癌症）治疗的重要靶点，更在信号通路中发挥着关键作用。这类激酶的特征在于能够磷酸化丝氨酸、苏氨酸或酪氨酸残基，从而通过显著改变蛋白质构象及其与相互作用蛋白的结合亲和力，快速可逆地调控底物蛋白功能，驱动正常及病理状态下的细胞活动。PTKs主要分为两大类：一类为酪氨酸激酶，另一类为丝氨酸/苏氨酸激酶。其中酪氨酸激酶又可进一步分为两个亚群：受体酪氨酸激酶（RTKs）与非受体酪氨酸激酶（NRTKs）。这两类激酶在众多细胞功能中发挥着"开关"调控作用。 NRTKs在多种癌症类型中呈现过表达与异常激活状态，通过细胞外信号依赖机制调控多样化的细胞功能。NRTKs介导的不同细胞功能可通过激酶依赖性或非依赖性机制，在细胞质或细胞核内进行精密调控。因此，靶向NRTKs对于改进多种肿瘤类型的治疗策略具有重要意义。本综述系统阐述NRTKs在肿瘤进展与耐药性中的结构基础与作用机制，并探讨其作为肿瘤治疗靶点的重要价值。
肿瘤(癌症)患者之家