Receptor tyrosine kinases (RTKs) are signaling enzymes responsible for the transfer of Adenosine triphosphate (ATP) γ-phosphate to the tyrosine residues substrates. RTKs demonstrate essential roles in cellular growth, metabolism, differentiation, and motility. Anomalous expression of RTK customarily leads to cell growth dysfunction, which is connected to tumor takeover, angiogenesis, and metastasis. Understanding the structure, mechanisms of adaptive and acquired resistance, optimizing inhibition of RTKs, and eradicating cum minimizing the havocs of quiescence cancer cells is paramount. Tyrosine kinase inhibitors (TKIs) vie with RTKs ATP-binding site for ATP and hitherto reduce tyrosine kinase phosphorylation, thus hampering the growth of cancer cells. TKIs can either be monoclonal antibodies that compete for the receptor’s extracellular domain or small molecules that inhibit the tyrosine kinase domain and prevent conformational changes that activate RTKs. Progression of cancer is related to aberrant activation of RTKs due to due to mutation, excessive expression, or autocrine stimulation. Understanding the modes of inhibition and structures of RTKs is germane to the design of novel and potent TKIs. This review shed light on the structures of tyrosine kinases, receptor tyrosine kinases, tyrosine kinase inhibitors, minimizing imatinib associated toxicities, optimization of tyrosine kinase inhibition in curtailing quiescence in cancer cells and the prospects of receptor tyrosine kinase based treatments.

中文翻译：

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探索癌症治疗中的受体酪氨酸激酶抑制剂

受体酪氨酸激酶 (RTK) 是负责将三磷酸腺苷 (ATP) γ-磷酸转移到酪氨酸残基底物的信号酶。RTK 在细胞生长、代谢、分化和运动中发挥着重要作用。RTK 的异常表达通常会导致细胞生长功能障碍，这与肿瘤接管、血管生成和转移有关。了解适应性和获得性耐药的结构、机制、优化对 RTK 的抑制以及根除并最大限度地减少静止癌细胞的破坏至关重要。酪氨酸激酶抑制剂 (TKIs) 与 RTK 的 ATP ATP 结合位点争夺 ATP，迄今为止减少酪氨酸激酶磷酸化，从而阻碍癌细胞的生长。TKI 可以是竞争受体胞外域的单克隆抗体，也可以是抑制酪氨酸激酶域并阻止激活 RTK 的构象变化的小分子。由于突变、过度表达或自分泌刺激，癌症的进展与 RTK 的异常激活有关。了解抑制模式和 RTK 的结构与新型有效 TKI 的设计密切相关。这篇综述阐明了酪氨酸激酶、受体酪氨酸激酶、酪氨酸激酶抑制剂的结构、最小化伊马替尼相关的毒性、优化酪氨酸激酶抑制以减少癌细胞的静止以及基于受体酪氨酸激酶的治疗前景。