Клинически значимые молекулярные мутации опухолей у собак и кошек: современное состояние диагностики, прогностической оценки и таргетной терапии

В последние годы молекулярная ветеринарная онкология развивается особенно активно благодаря внедрению современных методов геномного и транскриптомного анализа опухолей у животных. Мутации и сигнальные пути канцерогенеза становятся важными биомаркерами, позволяющими уточнять биологию опухолей, повышать точность диагностики, проводить прогностическую оценку и обосновывать применение таргетной терапии. Целью настоящего обзора является анализ современных данных о клинически значимых мутациях опухолей у собак и кошек и их роли в диагностике, прогностической оценке и лечении. В статье рассматриваются наиболее изученные молекулярные мишени, включая KIT, BRAF, HER2, PIK3CA и TP53, а также связанные с ними сигнальные пути опухолевого роста. Обобщены сведения о применении методов молекулярной диагностики, таких как полимеразная цепная реакция, иммуногистохимия, высокопроизводительное секвенирование и жидкостная биопсия. Особое внимание уделено значению молекулярных маркеров для сравнительной онкологии и перспективам интеграции многоомного профилирования опухолей в клиническую ветеринарную практику. Полученные данные свидетельствуют о формировании основ прецизионной ветеринарной онкологии, направленной на разработку более индивидуализированных стратегий диагностики и терапии опухолевых заболеваний у собак и кошек.

1. Aupperle-Lellbach H., Kehl A., de Brot S., van der Weyden L. Clinical Use of Molecular Biomarkers in Canine and Feline Oncology: Current and Future. Veterinary Sciences. 2024; 11(5): 199.https://doi.org/10.3390/vetsci11050199

2. Alshammari A.H. et al. Advancing Veterinary Oncology: NextGeneration Diagnostics for Early Cancer Detection and Clinical Implementation. Animals. 2025; 15(3): 389. https://doi.org/10.3390/ani15030389

3. De Biase D. et al. Investigation of the Theragnostic Role of KIT Expression for the Treatment of Canine Mast Cell Tumors with Tyrosine Kinase Inhibitors. Veterinary Sciences. 2024; 11(10): 492. https://doi.org/10.3390/vetsci11100492

4. Montanucci L. et al. Mutational Landscape of KIT Proto-Oncogene Coding Sequence in 62 Canine Cutaneous and Subcutaneous Mast Cell Tumors. Veterinary Sciences. 2024; 11(12): 593. https://doi.org/10.3390/vetsci11120593

5. Puget C. et al. Artificial intelligence predicts c-KIT exon 11 genotype by phenotype in canine cutaneous mast cell tumors: Can human observers learn it?. Veterinary Pathology. 2026; 63(2): 369‒379. https://doi.org/10.1177/03009858251380284

6. de Moura F.B.C., Amorim R.L., Fonseca-Alves C.E. Tyrosine kinase inhibitors in canine solid tumours: a systematic review of indications, response and safety. Veterinary Oncology. 2025; 2: 21. https://doi.org/10.1186/s44356-025-00036-1

7. Mochizuki H., Shapiro S.G., Breen M. Detection of BRAF Mutation in Urine DNA as a Molecular Diagnostic for Canine Urothelial and Prostatic Carcinoma. PLOS One. 2015; 10(12): e0144170. https://doi.org/10.1371/journal.pone.0144170

8. Aeschlimann L. et al. Effective detection of BRAFV595E mutation in canine urothelial and prostate carcinomas using immunohistochemistry. Veterinary and Comparative Oncology. 2024; 22(2): 295‒302. https://doi.org/10.1111/vco.12978

9. Appenzeller M., Kehl A., Törner K., Jensen K.C., Klopfleisch R., Aupperle-Lellbach H. BRAF Mutation Analysis: A Retrospective Evaluation of 8365 Diagnostic Samples with a Special View on Canine Breeds (2018–2024). Veterinary Sciences. 2025; 12(8): 729.https://doi.org/10.3390/vetsci12080729

10. Kehl A., Aupperle-Lellbach H., Brockmann M., van de Weyer A.-L., Appenzeller M., Steiger K. Utility of Urinary miRNA Biomarkers for Canine Urothelial Carcinoma Diagnostics. Veterinary Sciences. 2025; 12(7): 621. https://doi.org/10.3390/vetsci12070621

11. Lorch G. et al. Identification of Recurrent Activating HER2 Mutations in Primary Canine Pulmonary Adenocarcinoma. Clinical Cancer Research. 2019; 25(19): 5866‒5877. https://doi.org/10.1158/1078-0432.CCR-19-1145

12. Brunetti B. et al. Protein Expression, Amplification, and Mutation of HER2 Gene in Canine Primary Pulmonary Adenocarcinomas: Preliminary Results. Animals. 2024; 14(18): 2625. https://doi.org/10.3390/ani14182625

13. Marcinowska A., Horta R.D.S., Queiroga F., Giuliano A. Canine lung carcinoma—A descriptive review. Frontiers in Veterinary Science. 2025; 11: 1464659. https://doi.org/10.3389/fvets.2024.1464659

14. Vazquez E., Lipovka Y., Cervantes-Arias A., Garibay-Escobar A., Haby M.M., Queiroga F.L., Velazquez C. Canine Mammary Cancer: State of the Art and Future Perspectives. Animals. 2023; 13(19): 3147. https://doi.org/10.3390/ani13193147

15. Arendt M.L. et al. PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia. Scientific Reports. 2023; 13: 632. https://doi.org/10.1038/s41598-023-27664-7

16. Seung B.-J., Sur J.-H. Detection of PIK3CA hotspot mutations in canine mammary tumors using droplet digital PCR: tissue validation and liquid biopsy feasibility. Scientific Reports. 2024; 14: 25587. https://doi.org/10.1038/s41598-024-76820-0

17. Yeom J., Cho Y., Ahn S., Jeung S. Anticancer effects of alpelisib on PIK3CA-mutated canine mammary tumor cell lines. Frontiers in Veterinary Science. 2023; 10: 1279535. https://doi.org/10.3389/fvets.2023.1279535

18. Mei C. et al. Dysregulated Signaling Pathways in Canine Mammary Tumor and Human Triple Negative Breast Cancer: Advances and Potential Therapeutic Targets. International Journal of Molecular Sciences. 2025; 26(1): 145. https://doi.org/10.3390/ijms26010145

19. Rodrigues-Jesus J., Vilhena H., Canadas-Sousa A., Dias-Pereira P. Feline Mammary Tumors: A Comprehensive Review of Histological Classification Schemes, Grading Systems, and Prognostic Factors. Veterinary Sciences. 2025; 12(8): 736. https://doi.org/10.3390/vetsci12080736

20. Franco M. et al. PD-1, PD-L1, and PD-L2 Expression as Predictive Markers in Rare Feline Mammary Tumors. Veterinary Sciences. 2025; 12(8): 731. https://doi.org/10.3390/vetsci12080731

21. Tutu P. et al. Feline oral squamous cell carcinoma: recent advances and future perspectives. Frontiers in Veterinary Science. 2025; 12: 1663990. https://doi.org/10.3389/fvets.2025.1663990

22. Altamura G., Borzacchiello G. Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines. Frontiers in Veterinary Science. 2022; 9: 1040552. https://doi.org/10.3389/fvets.2022.1040552

23. Rodney A.R. et al. Genomic landscape and gene expression profiles of feline oral squamous cell carcinoma. Frontiers in Veterinary Science. 2023; 10: 1079019. https://doi.org/10.3389/fvets.2023.1079019

24. Vanhaezebrouck I.F., Bakhle K.M., Mendez-Valenzuela C.R., Lyle L.T., Konradt K., Scarpelli M.L. Single institution study of the immune landscape for canine oral melanoma based on transcriptome analysis of the primary tumor. Frontiers in Veterinary Science. 2023; 10: 1285909. https://doi.org/10.3389/fvets.2023.1285909

25. Mucignat G. et al. A Whole-Transcriptomic Analysis of Canine Oral Melanoma: A Chance to Disclose the Radiotherapy Effect and Outcome-Associated Gene Signature. Genes. 2024; 15(8): 1065. https://doi.org/10.3390/genes15081065

26. Dagli M.L.Z. et al. Identification of mutations in canine oral mucosal melanomas by exome sequencing and comparison with human melanomas. Scientific Reports. 2024; 14: 24174. https://doi.org/10.1038/s41598-024-74748-z

27. Mannheimer J.D. et al. Transcriptional profiling of canine osteosarcoma identifies prognostic gene expression signatures with translational value for humans. Communications Biology. 2023; 6: 856. https://doi.org/10.1038/s42003-023-05208-z

28. Das S. et al. Immune pathways and TP53 missense mutations are associated with longer survival in canine osteosarcomaa. Communications Biology. 2021; 4: 1178. https://doi.org/10.1038/s42003-021-02683-0

29. Weber M. et al. Transcriptomic and proteomic profiling identifies feline fibrosarcoma as clinically amenable model for aggressive sarcoma subtypes. Neoplasia. 2025; 60: 101104. https://doi.org/10.1016/j.neo.2024.101104

30. Megquier K. et al. Impact of preanalytical factors on liquid biopsy in the canine cancer model. bioRxiv. 2024; 605605. https://doi.org/10.1101/2024.07.29.605605

31. Chu K.T., Nekouei O., Giuliano A. Treatment outcomes of dogs with transitional cell carcinoma. Frontiers in Veterinary Science. 2025; 12: 1486786. https://doi.org/10.3389/fvets.2025.1486786

32. Dolnicka A., Fosse V., Raciborska A., Śmieszek A. Building a Therapeutic Bridge Between Dogs and Humans: A Review of Potential Cross-Species Osteosarcoma Biomarkers. International Journal of Molecular Sciences. 2025; 26(11): 5152. https://doi.org/10.3390/ijms26115152

33. Fenger JM, London CA, Kisseberth WC. Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology. ILAR J. 2014;55(1):69-85. https://doi:10.1093/ilar/ilu009.

34. Arendt M.L., van der Heiden A.D., Pensch R., Lindblad-Toh K. Genetics of canine cancer: a guide for the veterinary oncologist. Veterinary Oncology. 2025; 2: 9. https://doi.org/10.1186/s44356-025-00021-8

35. McDonald C., Taylor D., Linacre A. PCR in Forensic Science: A Critical Review. Genes. 2024; 15(4): 438. https://doi.org/10.3390/genes15040438

36. I saic A. et al. Next-Generation Sequencing: A Review of Its Transformative Impact on Cancer Diagnosis, Treatment, and Resistance Management. Diagnostics. 2025; 15(19): 2425. https://doi.org/10.3390/diagnostics15192425

37. Ramos-Vara J.A., Miller M.A. When tissue antigens and antibodies get along: revisiting the technical aspects of immunohistochemistrythe red, brown, and blue technique. Veterinary Pathology. 2014; 51(1): 42‒87. https://doi.org/10.1177/0300985813505879

38. Provenzano G. et al. Altered Expression of GABAergic Markers in the Forebrain of Young and Adult Engrailed-2 Knockout Mice. Genes. 2020; 11(4): 384. https://doi.org/10.3390/genes11040384

39. Smail C., Montgomery S.B. RNA Sequencing in Disease Diagnosis. Annual Review of Genomics and Human Genetics. 2024; 25: 353‒367. https://doi.org/10.1146/annurev-genom-021623-121812

40. Ludwig L., Dobromylskyj M., Wood G.A., van der Weyden L. Feline Oncogenomics: What Do We Know about the Genetics of Cancer in Domestic Cats?. Veterinary Sciences. 2022; 9(10): 547. https://doi.org/10.3390/vetsci9100547

41. Hartmann K et al. Feline Injection-Site Sarcoma and Other Adverse Reactions to Vaccination in Cats. Viruses. 2023; 15(8): 1708. https://doi.org/10.3390/v15081708

42. Lin J., Kouznetsova V.L., Tsigelny I.F. Molecular Mechanisms of Feline Cancers. OBM Genetics. 2021; 5(2). https://doi.org/10.21926/obm.genet.2102131

43. Wojtkowska A et al. Comparison of MMP-2, MMP-9, COX-2, and PGP Expression in Feline Injection-Site and Feline Noninjection-Site Sarcomas-Pilot Study. Animals (Basel). 2024 Jul 19;14(14):2110. https://doi:10.3390/ani14142110.

44. Wan J. et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nature Reviews Cancer. 2017; 17(4): 223–238.тhttps://doi.org/10.1038/nrc.2017.7