Pre-Clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review

Round 1

Reviewer 1 Report

The manuscript by Johnson et al. “Pre-clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review” discusses the recent advances on the translational science regarding MPM. While reading the aforementioned review I noticed that it is well structured. I believe that the manuscript is a good addition to the field, since it covers a wide range of bibliography for MPM and therefore can be used as a future reference in the field. I have the following specific recommendations:

1) (line 142) The physiological role of BAP1 should be further explained

2) (line 171) Cell cycle progression genes are presented in this section. The role of these genes should be mentioned in the MS.

3) (line 158) 41% and 58% (…add, respectively)

4) I believe that in Table 1 the field function should be mention SPECIFIC function (not oncogene, oncomiR etc.). Based on the GENERAL function, the Table should be separated into subsections including oncogenes, tumor suppressors, oncomiRs, etc.

5) in Table 2, in addition to the terms High, Low etc. in fields Sensitivity and Specificity, is it possible to add percentages?   

6) (line 590) this is an extremely big paragraph. I think that discussion on BAP1 should be on a separate paragraph to that of CDKN2A.

Author Response

We thank the reviewers comment, point-by-point response has been prepared and attached here for your further review. 

Author Response File: Author Response.docx

Reviewer 2 Report

The authors aimed to provide a comprehensive and updated review for pre-clinical research developments relating to improving the diagnosis and treatment of malignant pleural mesothelioma (MPM).  This manuscript in general has achieved the goal; however, the following comments are provided for the authors to improve the quality and understanding of potential readers.  

1. The strategies of literature review and inclusion criteria for papers selected are needed in the review.
2.  "To date, only the FDA- and European Medicines Agency (EMA)-approved cisplatin pemetrexed combination is used in frontline therapy, having demonstrated a modest in creased median survival from 9 to 12 months in most advanced stage MPM patients who are not eligible for surgery (125)."  The authors might omit a recent advance in treatment. The Food and Drug Administration approved the combination of nivolumab plus ipilimumab as first-line treatment for adult patients with unresectable malignant pleural mesothelioma in October 2020. [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-and-ipilimumab-unresectable-malignant-pleural-mesothelioma]. Some relevant papers need to be cited, such as [Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397:375–86.] 
3. The potential role of arginine-degrading agent PEGylated arginine deiminase may be needed to be addressed in this review.
4. The display of treatment development seems lengthy and complicated. Could the authors consider to provide summary tables of previously completed and current key clinical trials? It will benefit in-depth understanding of readers.  

Author Response

We thank the reviewer's valuable comments, point-by-point response has been prepared as well as track changes main text for your further review. 

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The authors have satisfactorily reponded to all my comments and made the necessary changes to the manuscript. Thanks.