PONE-D-23-23808

Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: MCL is malignant disease with poor clinical outcomes. In this study, the authors have shown inhibiting SRC-3 using SI-10 and SI-12 effectively inhibit MCL cells growth. Using in vivo approaches, the authors have shown inhibiting SRC-3 increase overall survival suggesting the potential of SRC-3 inhibitor in treating MCL. In this paper, proper approaches and statistical analysis have been applied.

Reviewer #2: Wang et al report preclinical data on an steroid receptor coactivator SRC inhibitor, named SI-10, in mantle cell lymphoma cell lines, especially in venetoclax or ibrutinib resistant cell lines and in a patient derived and syngeneic mouse model. +

A new drug for ibru or ven resistant mantle cell lymphoma is relevant application.

Question 1 cell model

The ibrutinib or venetoclex resistance is artificially produced. Do you know, or have hints if this resistance is similar to resistance seen in patients ? Did you test and/or find BTK mutations. ?

Question 2 long-term toxicty

Was there a concern for cardiotoxicity, as mentioned on page 2 ? You noted no weight changes in long-term treated mice.

Did you check for lab abnormalities troponin and pro-BNP, ?

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Reviewer #1: No

Reviewer #2: No

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Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma

PONE-D-23-23808R1

Dear Dr. Wang,

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Kind regards,

Francesco Bertolini, MD, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: