CanLymphoRec: Estabelecendo o perfil da recidiva de DLBCL canino

Canine lymphoma is a common and heterogeneous type of cancer that affects dogs of different breeds, ages, and lifestyles. DLBCL is the most common type of lymphoma in dogs. It is similar to human non-Hodgkin lymphoma (NHL) in many aspects, such as clinical presentation, histopathology, molecular features, and response to therapy. In dogs, complete response (CR) rates are high (85 to 95%), the median survival times surrounds the 12 months and 20 to 25% of the animals are still alive 2 years after the diagnosis. However, the majority of dogs relapse with lethal, drug-resistant lymphoma. The fact that relapse is much more frequent in DLBCL than in NHL warrants further research into its causes. Facing this problem, a multidisciplinary approach is being used here to construct an unparalell canine lymphoma biobank, with the aim of: (1) uncovering the reason why some cDLBCL respond favourably to standard therapeutics, while others end up relapsing and causing death. (2) create lymphoma cell culture lines from fully characterized cDLBCL patients, untreated and after recidive, that will enable the development of novel treatments without requiring the use of further animals. (3) we wish to establish ctDNA as a novel predictor and/or prognostic biomarker in cDLBCL. The major novelty of this study will be the first use of spatial transcriptomics in canine lymphoma samples. We expect that the combination of an experimental design where we compare untreated versus relapsed samples in the context of using innovative transcriptomic data, determination of TME biomarkers and circulating biomarkers, will enable breakthrough knowledge into the biology of DLBCL relapse and how to prevent and treat it. Creating cell lines from the same patients can also advance histopathology assessment, prognostic capacity, biomarker discovery and accelerate the testing of new therapeutic targets in veterinary oncology, and with a potential for human medicine, considering a translational approach, without using further animals. In conclusion, we expect to advance current oncological practice and gain new biomarkers for diagnosis, disease management, prognosis, and potential therapeutical targets. Moreover, we intend to extensively characterise novel lymphoma cell lines produced from canine patients (which were also extensively characterised), enabling future study of novel therapeutical agents while reducing the use of experimental animals to do so.