Building a Therapeutic Bridge Between Dogs and Humans: A Review of Potential Cross-Species Osteosarcoma Biomarkers

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript attempts to provide a comprehensive review of biomarkers in osteosarcoma (OSA) and their potential translational value between human and canine disease models. While the topic is both important and timely, this review would be significantly strengthened by contextualizing osteosarcoma biomarker research within the broader field of comparative oncology. The authors should incorporate examples of successful human-canine biomarker research from other cancer types (such as mammary tumors, lymphoma, melanoma and mast cell tumors) to highlight both commonalities and unique aspects of the comparative approach in osteosarcoma.

 

Specifically, the paper should address:

1. How translational biomarker research in other cancers has led to concrete clinical advances in both species, providing a roadmap for osteosarcoma research
2. The unique aspects of osteosarcoma biology that make comparative approaches particularly valuable (shared microenvironment interactions, metastatic patterns, treatment challenges)
3. Critical evaluation of which comparative biomarker approaches from other cancers might be most applicable to osteosarcoma
4. A clear framework demonstrating how findings from comparative studies in other tumor types can inform methodology and interpretation in osteosarcoma biomarker research

By placing their review within this broader context, the authors would strengthen their argument for the "translational bridge" mentioned in their title and provide readers with a more comprehensive understanding of osteosarcoma's unique position within comparative oncology research.

Author Response

Please find the Review Report in the attached PDF file. 

 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors, the review is accurate and gives and provides a current overwer of the knowledge on OSA's biomarkers.

I suggest some emendments to make the manuscript ready for editing.

Please, use an impersonal verbal form for increasing scientific soundness of the manuscript (line 29, 87).

Please, write in italics "de novo" as it is a Latin locution.

 Line 169 - I suggest to write also "and immunohistochemical (Vimentin)" after the word histopathological

Lime 251 - Please, cite at leat one  reference

Line 258 - Please, cite at least one reference

Line 451 - Plaese, cite the missing author "The study by ??? et al."

Chapter " 10. Radiological findings ..." - I suggest to highlight that diagnostic imaging are also an important tools for targeted sampling for supporting an accurate histomorphological in oncology diagnostic. 

 

 

Author Response

Please find the Review Report in the attached PDF file. 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript is well written and organized, I suggest publication after minor revision.  

1.It appears that the authors used BioRender to prepare their figures. According to BioRender's user guidelines, it is important to properly acknowledge its use to avoid potential copyright issues in the future.

2.On page 5, line 178, the authors state: “In dogs, the disease progresses more rapidly due to their accelerated biology, allowing researchers to study treatment responses and disease outcomes over a shorter time.” While this highlights the advantages of using dogs as a model for disease progression, it is equally important to discuss the limitations or disadvantages of this model to provide a more balanced and objective perspective.

3.The authors should include a reference to support the claim on page 8, line 327: “It is worth noting that the diagnostic potential of miR-21 is strongly recognized in canine mast cell tumors (MCTs), as it can distinguish between healthy and MCT-affected dogs, differentiate tumor origin (cutaneous vs. subcutaneous), and identify metastatic status, underscoring its value as a minimally invasive tool for detecting epigenetic alterations in canine tumors.”

4.Additional references are needed to support the statement on page 4, line 160: “For instance, medicine utilizes a broader spectrum of targeted imaging techniques, including enhanced MRI protocols and innovative radiotracers for PET scans.

Author Response

Please find the Review Report in the attached PDF file. 

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

Considering that osteosarcoma is a disabling tumor with similar evolution in humans and dogs, the use of the dog as an experimental model for prevention, diagnosis and development of therapies is an important goal considering the severity of the prognosis.

The present work very critically and coherently approaches the incidence and prevalence of the disease, the symptomatology but especially emphasizes its genetic polymorphism which is difficult to control due to genetic instability. As you have highlighted, the identification of representative biomarkers for early diagnosis and targeted treatment would lead to an increase in life expectancy in both species.

Author Response

Please find the Review Report in the attached PDF file. 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript has been appropriately revised and added in accordance with the reviewers' suggestions, and is considered suitable for publication in this journal.