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

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2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9-24
Number of pages16
JournalVeterinary and Comparative Oncology
Volume18
Issue number1
DOIs
StatePublished - Mar 1 2020

Bibliographical note

Funding Information:
The authors wish to thank Dr Jaime Modiano for his thoughtful comments as well as the Comparative Oncology Group, the Clinical Investigation Center, the oncology/radiation oncology nurses who help provide opportunities and care for our canine patients, and the clients and pets who participate in studies to advance sarcoma care. This work was supported by grant K01OD017242 (A.B.) from the Office of The Director, National Institutes of Health, grant AB15MN-002 from the National Canine Cancer Foundation (A.B.), a grant from the Masonic Cancer Center, University of Minnesota Sarcoma Translational Working Group (A.B.), the Skippy Frank Fund for Life Sciences and Translational Research (A.B., J.L., E.B.D.), the Rein in Sarcoma Foundation (A.B., J.L., E.B.D.), the Sarcoma Foundation of America (E.B.D.), and Morris Animal Foundation (D18CA-017, E.B.D.). The authors gratefully acknowledge generous support from the Angiosarcoma Awareness Foundation and donations to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project.

Funding Information:
The authors wish to thank Dr Jaime Modiano for his thoughtful comments as well as the Comparative Oncology Group, the Clinical Investigation Center, the oncology/radiation oncology nurses who help provide opportunities and care for our canine patients, and the clients and pets who participate in studies to advance sarcoma care. This work was supported by grant K01OD017242 (A.B.) from the Office of The Director, National Institutes of Health, grant AB15MN‐002 from the National Canine Cancer Foundation (A.B.), a grant from the Masonic Cancer Center, University of Minnesota Sarcoma Translational Working Group (A.B.), the Skippy Frank Fund for Life Sciences and Translational Research (A.B., J.L., E.B.D.), the Rein in Sarcoma Foundation (A.B., J.L., E.B.D.), the Sarcoma Foundation of America (E.B.D.), and Morris Animal Foundation (D18CA‐017, E.B.D.). The authors gratefully acknowledge generous support from the Angiosarcoma Awareness Foundation and donations to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project.

Publisher Copyright:
© 2019 John Wiley & Sons Ltd

Keywords

  • cancer
  • canine
  • checkpoint inhibitor
  • epidermal growth factor receptor
  • radiation therapy
  • sarcoma
  • toxin
  • urokinase plasminogen activator receptor, propranolol
  • vaccine

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