MiRNA profiling in 3D tumoroid models: a powerful platform for targeted mammary cancer therapy in dogs

Canine mammary tumors (CMTs) are one of the most common carcinomas affecting female dogs. Despite advancements in veterinary care, challenges persist in achieving early diagnosis and implementing effective systematic therapy. Particularly, small non-coding microRNAs (miRNAs) involved in gene regulation represent an attractive group of biomarkers. Thus, early clinical diagnosis of CMTs with specific biomarkers and the development of tumor-specific targeted treatments via 3D tumoroid modeling offers an opportunity for improved clinical outcomes for oncologic patients. Nowadays, pyrrolidines have been highlighted as molecules with promising anticancer potential, including CMTs. The goal of the project is the identification and analysis of changes in miRNA expression levels in situ (in mammary gland tumors) and in 3D model systems derived from CMTs. Subsequently, these 3D tumoroids will be used to monitor the antiproliferative and pro-apoptotic effect of new pyrrolidine derivates. The compounds with the highest antitumor activity will be selected for the adjuvant-secondary therapy for dogs with CMT. Developing specific biomarkers for early diagnosis and prognosis and targeted personalized medicine is crucial in veterinary oncology. Combining miRNA profiling with testing of new molecules based on pyrrolidines in patient-specific tumoroids can advance personalized treament for dogs with mammary cancer, leading to more effective and tailored therapy.