Tarone Lidia, Mareschi Katia, Tirtei Elisa, Giacobino Davide, Camerino Mariateresa, Buracco Paolo, Morello Emanuela, Cavallo Federica, Riccardo Federica
Molecular Biotechnology Center "Guido Tarone", Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
Department of Public Health and Paediatrics, University of Torino, Piazza Polonia 94, 10126 Torino, Italy.
Life (Basel). 2022 Dec 14;12(12):2099. doi: 10.3390/life12122099.
Osteosarcoma (OSA) is the most common pediatric malignant bone tumor. Although surgery together with neoadjuvant/adjuvant chemotherapy has improved survival for localized OSA, most patients develop recurrent/metastatic disease with a dismally poor outcome. Therapeutic options have not improved for these OSA patients in recent decades. As OSA is a rare and "orphan" tumor, with no distinct targetable driver antigens, the development of new efficient therapies is still an unmet and challenging clinical need. Appropriate animal models are therefore critical for advancement in the field. Despite the undoubted relevance of pre-clinical mouse models in cancer research, they present some intrinsic limitations that may be responsible for the low translational success of novel therapies from the pre-clinical setting to the clinic. From this context emerges the concept of comparative oncology, which has spurred the study of pet dogs as a uniquely valuable model of spontaneous OSA that develops in an immune-competent system with high biological and clinical similarities to corresponding human tumors, including in its metastatic behavior and resistance to conventional therapies. For these reasons, the translational power of studies conducted on OSA-bearing dogs has seen increasing recognition. The most recent and relevant veterinary investigations of novel combinatorial approaches, with a focus on immune-based strategies, that can most likely benefit both canine and human OSA patients have been summarized in this commentary.
骨肉瘤（OSA）是最常见的儿童恶性骨肿瘤。尽管手术联合新辅助/辅助化疗提高了局限性OSA患者的生存率，但大多数患者仍会出现复发/转移性疾病，预后极差。近几十年来，这些OSA患者的治疗选择并未得到改善。由于OSA是一种罕见的“孤儿”肿瘤，没有明确的可靶向驱动抗原，开发新的有效疗法仍然是一项未满足且具有挑战性的临床需求。因此，合适的动物模型对于该领域的进展至关重要。尽管临床前小鼠模型在癌症研究中具有毋庸置疑的相关性，但它们存在一些内在局限性，这可能是新疗法从临床前阶段到临床转化成功率低的原因。在此背景下，比较肿瘤学的概念应运而生，它推动了将宠物狗作为自发OSA的独特有价值模型的研究，这种模型在免疫健全的系统中发展，与相应的人类肿瘤在生物学和临床方面具有高度相似性，包括其转移行为和对传统疗法的抗性。出于这些原因，对携带OSA的狗进行的研究的转化能力得到了越来越多的认可。本评论总结了最新且相关的兽医研究，这些研究聚焦于新型联合方法，尤其是基于免疫的策略，这些策略极有可能使犬类和人类OSA患者均受益。
