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靶向治疗癌症受体酪氨酸激酶的治疗进展。

Therapeutic advances of targeting receptor tyrosine kinases in cancer.

机构信息

Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.

出版信息

Signal Transduct Target Ther. 2024 Aug 14;9(1):201. doi: 10.1038/s41392-024-01899-w.

Abstract

Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role in cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression of certain RTKs, are critical in creating environments conducive to tumor development. Following their discovery, extensive research has revealed how RTK dysregulation contributes to oncogenesis, with many cancer subtypes showing dependency on aberrant RTK signaling for their proliferation, survival and progression. These findings paved the way for targeted therapies that aim to inhibit crucial biological pathways in cancer. As a result, RTKs have emerged as primary targets in anticancer therapeutic development. Over the past two decades, this has led to the synthesis and clinical validation of numerous small molecule tyrosine kinase inhibitors (TKIs), now effectively utilized in treating various cancer types. In this manuscript we aim to provide a comprehensive understanding of the RTKs in the context of cancer. We explored the various alterations and overexpression of specific receptors across different malignancies, with special attention dedicated to the examination of current RTK inhibitors, highlighting their role as potential targeted therapies. By integrating the latest research findings and clinical evidence, we seek to elucidate the pivotal role of RTKs in cancer biology and the therapeutic efficacy of RTK inhibition with promising treatment outcomes.

摘要

受体酪氨酸激酶(RTKs)是一类跨膜受体,由于其在癌症发病机制中的核心作用,在肿瘤学中引起了广泛关注。包括突变、扩增和某些 RTK 的过表达在内的遗传改变,对于创造有利于肿瘤发展的环境至关重要。在发现 RTKs 后,广泛的研究揭示了 RTK 失调如何导致肿瘤发生,许多癌症亚型显示出对异常 RTK 信号的依赖性,以维持其增殖、存活和进展。这些发现为旨在抑制癌症中关键生物学途径的靶向治疗铺平了道路。因此,RTKs 已成为抗癌治疗开发的主要靶点。在过去的二十年中,这导致了许多小分子酪氨酸激酶抑制剂(TKI)的合成和临床验证,现在它们有效地用于治疗各种癌症类型。在本文中,我们旨在全面了解癌症中的 RTKs。我们探讨了不同恶性肿瘤中特定受体的各种改变和过表达,特别关注当前 RTK 抑制剂的检查,强调它们作为潜在靶向治疗的作用。通过整合最新的研究发现和临床证据,我们试图阐明 RTKs 在癌症生物学中的关键作用以及 RTK 抑制的治疗效果,为患者带来有希望的治疗结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48de/11323831/e8c78bd005ea/41392_2024_1899_Fig1_HTML.jpg

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