London Cheryl A
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Top Companion Anim Med. 2009 Aug;24(3):106-12. doi: 10.1053/j.tcam.2009.02.002.
Substantial progress in the field of molecular biology has permitted the identification of key abnormalities in cancer cells involving cell proteins that regulate signal transduction, cell survival, and cell proliferation. Such abnormalities often involve a class of proteins called tyrosine kinases that act to phosphorylate other proteins in the cell, tightly regulating a variety of cellular processes. A variety of small molecule inhibitors that target specific tyrosine kinases (known as tyrosine kinase inhibitors [TKIs]) have now been approved for the treatment of human cancer, and it is likely many more will become available in the near future. In some instances these inhibitors have exhibited significant clinical efficacy, and it is likely their biologic activity will be further enhanced as combination regimens with standard treatment modalities are explored. Although TKIs have been used extensively in humans, their application to cancers in dogs and cats is relatively recent. The TKIs Palladia (toceranib), Kinavet (masitinib), and Gleevec (imatinib) have been successfully used in dogs, and more recently Gleevec in cats. This article will review the biology of tyrosine kinase dysfunction in human and animal cancers, and the application of specific TKIs to veterinary cancer patients.
分子生物学领域的重大进展使得人们能够识别癌细胞中的关键异常，这些异常涉及调节信号转导、细胞存活和细胞增殖的细胞蛋白。此类异常通常涉及一类名为酪氨酸激酶的蛋白质，它们可使细胞中的其他蛋白质磷酸化，从而严格调控多种细胞过程。目前，多种靶向特定酪氨酸激酶的小分子抑制剂（称为酪氨酸激酶抑制剂 [TKI]）已被批准用于治疗人类癌症，并且在不久的将来可能会有更多此类药物问世。在某些情况下，这些抑制剂已显示出显著的临床疗效，随着与标准治疗方式联合方案的探索，其生物学活性可能会进一步增强。尽管TKI已在人类中广泛使用，但它们在犬猫癌症中的应用相对较新。TKI药物帕拉迪（托西替尼）、基纳韦特（马西替尼）和格列卫（伊马替尼）已成功用于犬类治疗，最近格列卫也用于猫类治疗。本文将综述人类和动物癌症中酪氨酸激酶功能障碍的生物学机制，以及特定TKI在兽医癌症患者中的应用。
