Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

Abstract

Sarcomas represent a group of genomically chaotic, highly heterogenous tumours of mesenchymal origin with variable mutational load. Conventional therapy with surgery and radiation therapy is effective for managing small, low‐grade sarcomas and remains the standard therapeutic approach. For advanced, high‐grade, recurrent, or metastatic sarcomas, systemic chemotherapy provides minimal benefit, therefore, there is a drive to develop novel approaches. The discovery of “Coley's toxins” in the 19th century, and their use to stimulate the immune system supported the application of unconventional therapies for the treatment of sarcomas. While promising, this initial work was abandoned and treatment paradigm and disease course of sarcomas was largely unchanged for several decades. Exciting new therapies are currently changing treatment algorithms for advanced carcinomas and melanomas, and similar approaches are being applied to advance the field of sarcoma research. Recent discoveries in subtype‐specific cancer biology and the identification of distinct molecular targets have led to the development of promising targeted strategies with remarkable potential to change the landscape of sarcoma therapy in dogs. The purpose of this review article is to describe the current standard of care and limitations as well as emerging approaches for sarcoma therapy that span many of the most active paradigms in oncologic research, including immunotherapies, checkpoint inhibitors, and drugs capable of cellular metabolic reprogramming.

Outcome with surgical treatment of canine soft tissue sarcoma in the region of the ischiatic tuberosity: A veterinary society of surgical oncology retrospective study

“…These studies found that low-grade STS (grade I or II) are unlikely to recur, and when they do, the slow-growing nature of the tumours allows for more conservative management and less impact on overall patient quality of life. Highgrade (grade III) STS are more likely to recur 1,[42][43][44] and have increased risk for metastatic spread with reported rates of 22%-44%. [33][34][35]45 The findings of this study support previous reports of low-grade STS having a low risk of recurrence and metastatic spread as DFI and PFI were reached only with grade III tumours.…”

“…Soft tissue sarcoma (STS) is a spontaneously occurring connective‐tissue tumour in animals and humans 1 . True incidence of STS in dogs is unknown but it has been previously suggested that these tumours account for 9%–15% of all cutaneous and subcutaneous canine tumours 1 . The underlying causes for sarcomas are varied and multifactorial 2–28 .…”

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

“…A consequence of increased Nor concentrations is higher concentrations of both MDSCs and TAMs in tumor tissues. For example, activation of b2-adrenergic receptor (b-AR) signaling was shown to upregulate STAT3 and NFk-b signaling pathways which drive development of immune suppressive MDSC and TAMs (199). Activation of b-AR signaling has been shown to polarize macrophages to an immunosuppressive M2 phenotype in a rodent breast cancer model (200,201).…”

Prognostic impact of clinical, haematological, and histopathological variables in 102 canine cutaneous perivascular wall tumours

“…The role of the systemic inflammatory response against cancer is widely accepted in human oncology and is becoming increasingly evident in small animal oncology as well 5 . Indeed, inflammation orchestrates tumour microenvironment, which is crucial for proliferation, survival and migration of cancer cells 6 .…”