PONE-D-24-19048Development of an in vivo syngeneic mouse transplant model of invasive intestinal adenocarcinoma driven by endogenous expression of Pik3caH1047R and Apc lossPLOS ONE

Dear Dr. Phillips,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

This is an interesting manuscript well performed and that opens insights on the possible use in cancer therapies. The Authors must highlight this aspect and add some info about human more recent studies on organoids and more recent use in therapies as specified to them by a reviewer and by myself in our reports.

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We look forward to receiving your revised manuscript.

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Gianpaolo Papaccio, M.D., Ph.D.

Academic Editor

PLOS ONE

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2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

https://link.springer.com/article/10.1007/s00384-018-3202-8?

https://www.pure.ed.ac.uk/ws/files/20002553/Mouse_models_of_colorectal_cancer_as_preclinical_models.pdf?

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"I have read the journal's policy and the authors of this manuscript have the following competing interests: 

Wayne A. Phillips is a member of the editorial board of PLOS ONE. The authors have declared that no other competing interests exist."

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Additional Editor Comments:

In this study, the Authors obtained an immunocompetent, transplantable model of colorectal cancer, that can be suitable for in vivo studies of immune-based therapies.

Albeit its interest, it must then evaluate the relationships with TME.

Taking into consideration that it is a murine model and not a human one, the Authors must add and focus in the human cancer field in order to give more interest to this study, adding several info on organoids and human colorectal cancer as well as proteo trascriptomics and TME ( J Exp Clin Cancer Res. 2023 Jan 6;42(1):8. doi: 10.1186/s13046-022-02591-z; doi: 10.3390/cancers12123611; ESMO Open Volume 5, Issue 523 September 2020 Article number e000847;International Journal of Molecular Sciences Volume 24, Issue 23December 2023 Article number 17101 etc).

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Reviewers' comments:

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Comments to the Author

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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: In this manuscript, the Authors generated an immunocompetent, transplantable model of colorectal cancer suitable for in vivo assessment of immune-based therapeutic approaches. The manuscript is interesting, and it is a starting point to develop a model by which it is possible to evaluate relationship among different cell types homing in the tumour microenvironment. Albeit this, the authors must better focus on how they want to exploit this model in human cancer field. Moreover, they must add information regarding the possibility to use other models as organoids for drug screening (citing the studies as J Exp Clin Cancer Res. 2023 Jan 6;42(1):8. doi: 10.1186/s13046-022-02591-z; doi: 10.3390/cancers12123611.) and tumour microenvironment evaluation.

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Reviewer #1: No

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Development of an in vivo syngeneic mouse transplant model of invasive intestinal adenocarcinoma driven by endogenous expression of Pik3caH1047R and Apc loss

PONE-D-24-19048R1

Dear Dr. Phillips,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Gianpaolo Papaccio, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The Authors made the minor amendments as requested

Reviewers' comments: