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犬血管肉瘤的新分子靶点——精准医学的比较性综述与未来展望

New molecular targets in canine hemangiosarcoma-Comparative review and future of the precision medicine.

作者信息

Kapturska Karolina Małgorzata, Pawlak Aleksandra

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.

Veterinary Clinic NEOVET s.c. Hildebrand, Jelonek, Michalek-Salt, Wroclaw, Poland.

出版信息

Vet Comp Oncol. 2023 Sep;21(3):357-377. doi: 10.1111/vco.12917. Epub 2023 Jun 12.

Abstract

Human angiosarcoma and canine hemangiosarcoma reveal similarities not only in their aggressive clinical behaviour, but especially in molecular landscape and genetic alterations involved in tumorigenesis and metastasis formation. Currently, no satisfying treatment that allows for achieving long overall survival or even prolonged time to progression does not exist. Due to the progress that has been made in targeted therapies and precision medicine the basis for a new treatment design is to uncover mutations and their functions as possible targets to provide tailored drugs for individual cases. Whole exome or genome sequencing studies and immunohistochemistry brought in the last few years important discoveries and identified the most common mutations with probably crucial role in this tumour development. Also, despite a lack of mutation in some of the culprit genes, the cancerogenesis cause may be buried in main cellular pathways connected with proteins encoded by those genes and involving, for example, pathological angiogenesis. The aim of this review is to highlight the most promising molecular targets for precision oncology treatment from the veterinary perspective aided by the principles of comparative science. Some of the drugs are only undergoing laboratory in vitro studies and others entered the clinic in the management of other cancer types in humans, but those used in dogs with promising responses have been mentioned as priorities.

摘要

人类血管肉瘤和犬血管肉瘤不仅在侵袭性临床行为上表现出相似性,尤其是在肿瘤发生和转移形成所涉及的分子格局和基因改变方面。目前,尚无令人满意的治疗方法能够实现长期总生存甚至延长疾病进展时间。由于靶向治疗和精准医学取得的进展,新治疗方案设计的基础是揭示突变及其功能,将其作为可能的靶点,为个体病例提供量身定制的药物。全外显子组或基因组测序研究以及免疫组化在过去几年带来了重要发现,并确定了在这种肿瘤发展中可能起关键作用的最常见突变。此外,尽管一些致病基因中没有突变,但致癌原因可能隐藏在与这些基因编码的蛋白质相关的主要细胞通路中,例如涉及病理性血管生成。本综述的目的是从兽医角度,借助比较科学原理,突出精准肿瘤治疗中最有前景的分子靶点。一些药物仅在实验室进行体外研究,其他药物已进入人类其他癌症类型的临床治疗,但在犬类中使用且有前景的药物已被优先提及。

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