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激酶在人类癌症进展中的病因学作用及其靶向策略

Etiologic Role of Kinases in the Progression of Human Cancers and Its Targeting Strategies.

作者信息

Das Sanjoy, Bhattacharya Bireswar, Das Biplajit, Sinha Bibek, Jamatia Taison, Paul Kishan

机构信息

Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam 786004 India.

Regional Institute of Pharmaceutical Science and Technology, Agartala, Tripura 799005 India.

出版信息

Indian J Surg Oncol. 2021 Apr;12(Suppl 1):34-45. doi: 10.1007/s13193-019-00972-z. Epub 2019 Aug 19.

Abstract

Cancer is one of the dominant causes of death worldwide while lifelong prognosis is still inauspicious. The maturation of the cancer is seen as a process of transformation of a healthy cell into a tumor-sensitive cell, which is held entirely at the cellular, molecular, and genetic levels of the organism. Tyrosine kinases can play a major, etiologic role in the inception of malignancy and devote to the uncontrolled proliferation of cancerous cells and the progression of a tumor as well as the development of metastatic disease. Angiogenesis and oncogene activation are the major event in cell proliferation. The growth of a tumor and metastasis are fully depending on angiogenesis and lymphangiogenesis triggered by chemical signals from tumor cells in a phase of rapid growth. Tyrosine kinase inhibitors are compounds that inhibit tyrosine kinases and effective in targeting angiogenesis and blocking the signaling pathways of oncogenes. Small molecule tyrosine kinase inhibitors like afatinib, erlotinib, crizotinib, gefitinib, and cetuximab are shown to a selective cut off tactic toward the constitutive activation of an oncogene in tumor cells, and thus contemplated as promising therapeutic approaches for the diagnosis of cancer and malignancies.

摘要

癌症是全球主要的死亡原因之一,而其终生预后仍然不容乐观。癌症的成熟被视为一个健康细胞转变为肿瘤敏感细胞的过程,这完全发生在生物体的细胞、分子和基因层面。酪氨酸激酶在恶性肿瘤的发生中可能起主要病因作用,并有助于癌细胞的不受控制增殖、肿瘤进展以及转移性疾病的发展。血管生成和癌基因激活是细胞增殖中的主要事件。肿瘤的生长和转移完全依赖于在快速生长阶段由肿瘤细胞的化学信号触发的血管生成和淋巴管生成。酪氨酸激酶抑制剂是抑制酪氨酸激酶的化合物,对靶向血管生成和阻断癌基因的信号通路有效。像阿法替尼、厄洛替尼、克唑替尼、吉非替尼和西妥昔单抗这样的小分子酪氨酸激酶抑制剂显示出对肿瘤细胞中癌基因组成型激活的选择性阻断策略,因此被视为癌症和恶性肿瘤诊断的有前景的治疗方法。

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