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酪氨酸激酶抑制剂及其获得性耐药的研究进展。

Advances in studies of tyrosine kinase inhibitors and their acquired resistance.

机构信息

International Biotechnology R&D Center, Shandong University School of Ocean, 180 Wenhua Xi Road, Weihai, Shandong, 264209, China.

School of Preclinical Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu, 210023, China.

出版信息

Mol Cancer. 2018 Feb 19;17(1):36. doi: 10.1186/s12943-018-0801-5.

Abstract

Protein tyrosine kinase (PTK) is one of the major signaling enzymes in the process of cell signal transduction, which catalyzes the transfer of ATP-γ-phosphate to the tyrosine residues of the substrate protein, making it phosphorylation, regulating cell growth, differentiation, death and a series of physiological and biochemical processes. Abnormal expression of PTK usually leads to cell proliferation disorders, and is closely related to tumor invasion, metastasis and tumor angiogenesis. At present, a variety of PTKs have been used as targets in the screening of anti-tumor drugs. Tyrosine kinase inhibitors (TKIs) compete with ATP for the ATP binding site of PTK and reduce tyrosine kinase phosphorylation, thereby inhibiting cancer cell proliferation. TKI has made great progress in the treatment of cancer, but the attendant acquired acquired resistance is still inevitable, restricting the treatment of cancer. In this paper, we summarize the role of PTK in cancer, TKI treatment of tumor pathways and TKI acquired resistance mechanisms, which provide some reference for further research on TKI treatment of tumors.

摘要

蛋白酪氨酸激酶(PTK)是细胞信号转导过程中的主要信号酶之一,它催化将 ATP-γ-磷酸转移到底物蛋白的酪氨酸残基上,使其磷酸化,调节细胞生长、分化、死亡和一系列生理生化过程。PTK 的异常表达通常导致细胞增殖紊乱,与肿瘤的侵袭、转移和肿瘤血管生成密切相关。目前,多种 PTKs 已被用作抗肿瘤药物筛选的靶点。酪氨酸激酶抑制剂(TKI)与 ATP 竞争 PTK 的 ATP 结合位点,降低酪氨酸激酶磷酸化,从而抑制癌细胞增殖。TKI 在癌症治疗方面取得了巨大进展,但随之而来的获得性耐药性仍然不可避免,限制了癌症的治疗。本文总结了 PTK 在癌症中的作用、TKI 治疗肿瘤的途径和 TKI 获得性耐药机制,为进一步研究 TKI 治疗肿瘤提供了一些参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9da/5817861/fbf03d6ae72e/12943_2018_801_Fig1_HTML.jpg

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