Review on Advanced Cancer Modeling for a Cancer Study
Round 1
Reviewer 1 Report
The title of the paper is "Review on advanced cancer modeling for cancer study" which suggest deep and essential review of broad world-wide literature in cancer biomathematical modeling. However, the presented article is a very shord and brief summary of most important and recent findings in that matter.
I have no comments to the meritorical aspects of the article which are scientifically sound and correct. My biggest concern is that the article is narrowed to single aspects of that important topic. My recommendation is to significantly implove the article, review the literature in cancer modeling because there are hundreds of models published which were note metioned by the author. Additionally, please review the literature connected with the Gompertz Law (function) which usually describes the proliferation of cancer cells. There is also a texbook "The physics of cancer" (La Porta and Zapperi, 2017) which is also worth to review.
From the technical point of view: it looks that the article is cut at the line 221, where the chapter "10. Results" shows one figure only, whithout text and conclusions.
Author Response
Point-by-point response to the reviewers
We appreciate the reviewers for their constructive comments for improvement of the manuscript. The revised manuscript is substantially improved by addressing reviewer’s comments. We hope that our revised manuscript is now suitable for publication in Current issues in molecular biology.
Reviewer’s comments
Reviewer #1.
The title of the paper is "Review on advanced cancer modeling for cancer study" which suggest deep and essential review of broad world-wide literature in cancer biomathematical modeling. However, the presented article is a very shord and brief summary of most important and recent findings in that matter.I have no comments to the meritorical aspects of the article which are scientifically sound and correct. My biggest concern is that the article is narrowed to single aspects of that important topic. My recommendation is to significantly implove the article, review the literature in cancer modeling because there are hundreds of models published which were note metioned by the author. Additionally, please review the literature connected with the Gompertz Law (function) which usually describes the proliferation of cancer cells. There is also a texbook "The physics of cancer" (La Porta and Zapperi, 2017) which is also worth to review.
-We appreciate reviewer’s constructive comments, we added several points to avoid narrowing point of views of that important topic. Given this manuscript is the opinion article, not a full-text review, focused on addressing recent cancer modeling for cancer study, especially in 3D tumor organoids, we shortly added introduced the contents of cancer modeling.
From the technical point of view: it looks that the article is cut at the line 221, where the chapter "10. Results" shows one figure only, whithout text and conclusions.
- As reviewer’s comments, we explain the figure 1 in introduction and result parts. In addition, we also make conclusion part to increase the completion of this manuscript. We hope that the reviewer #1 is satisfied with our revised version of manuscript.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Cancer cells heterogeneity is one of the most challenging aspects of tumor biology. There can be several kinds of heterogeneity: (i) genetic, (ii) protein expression, (iii) posttranslational protein modification (see the excellent review of Sun and Yu, 2015). The author focuses on the genetic alterations, only. This should be clearly stated in the introduction since cancer heterogeneity cannot be reduced to differences in stem cell genetics. Therefore, the statement in line 27 should be revised. Many statements are not well reflected, e.g. line 86-87: “The organoids are self-organized three-dimensional tissue cultures that are derived normal adult stem cells [20, 21, 41].” This statement is true only for part of the organoids used in recent research.
The review is sort of a listing of organoid models in different cancer types, lacking more specific and systematic information, e.g. on the methods used to establish and culture those organoids, the basic mechanisms of tumor biology investigated, or the success in drug screening done on PDTX organoids. There are many problems associated with PDTX organoids, especially in using them for drug screening in personalized therapies. The author state this in lines 58-59, but a critical discussion is missing. Are there studies proving the validity of this approach by demonstrating successful personalized therapeutic strategies in patients? Which tumor entities are the most promising in this respect?
In line 181, the author states: “Therefore, PDTX model systems is not suitable for high-throughput drug screening [15, 75].” Then in the next sentence: “Until now, tumor organoid are currently most effective application for drug screening.” This seems to be a clear contradiction.
A conclusion section is missing.
In this form the review does not add much to literature and is misleading in several respects.
Detailed concerns (examples)
· The abstract does not well reflect the content and results of the review. It is much too superficial.
· All abbreviations need the full term for explanation at first occurrence (e.g. line 32).
· line 32: “... mutation of APC ...” should read “... mutation of the APC (adenomatous polyposis coli) gene...”.
· line 39-40: missing citation number.
· line 89: What is the meaning of this sentence?
References:
Sun XX, Yu Q. Intra-tumor heterogeneity of cancer cells and its implications for cancer treatment. Acta Pharmacol Sin. 2015 Oct;36(10):1219-27. doi: 10.1038/aps.2015.92. Epub 2015 Sep 21. PMID: 26388155; PMCID: PMC4648179.
Author Response
Point-by-point response to the reviewers
We appreciate the reviewers for their constructive comments for improvement of the manuscript. The revised manuscript is substantially improved by addressing reviewer’s comments. We hope that our revised manuscript is now suitable for publication in Current issues in molecular biology.
Reviewer’s comments
Reviewer #2
Cancer cells heterogeneity is one of the most challenging aspects of tumor biology. There can be several kinds of heterogeneity: (i) genetic, (ii) protein expression, (iii) posttranslational protein modification (see the excellent review of Sun and Yu, 2015). The author focuses on the genetic alterations, only. This should be clearly stated in the introduction since cancer heterogeneity cannot be reduced to differences in stem cell genetics. Therefore, the statement in line 27 should be revised. Many statements are not well reflected, e.g. line 86-87: “The organoids are self-organized three-dimensional tissue cultures that are derived normal adult stem cells [20, 21, 41].” This statement is true only for part of the organoids used in recent research.
The review is sort of a listing of organoid models in different cancer types, lacking more specific and systematic information, e.g. on the methods used to establish and culture those organoids, the basic mechanisms of tumor biology investigated, or the success in drug screening done on PDTX organoids. There are many problems associated with PDTX organoids, especially in using them for drug screening in personalized therapies. The author state this in lines 58-59, but a critical discussion is missing. Are there studies proving the validity of this approach by demonstrating successful personalized therapeutic strategies in patients? Which tumor entities are the most promising in this respect?
In line 181, the author states: “Therefore, PDTX model systems is not suitable for high-throughput drug screening [15, 75].” Then in the next sentence: “Until now, tumor organoid are currently most effective application for drug screening.” This seems to be a clear contradiction.
A conclusion section is missing.
In this form the review does not add much to literature and is misleading in several respects.
We appreciate reviewer’s informative comments, we added many points to discuss more various aspects of recent advances in cancer modeling. To explain the general tumor heterogeneity, we added genetic, protein expression, and posttranslational protein modification in the development of tumoral heterogeneity. However, given this manuscript is the opinion article, not a full-text review article, focused on introducing recent cancer modeling for cancer study, we did not add the methodologic aspects. We also tried to improve the PDTX section, especially in tumoral heterogeneity. Although PDTX model system which we addressed in this opinion manuscript is Patient derived tumor xenograft not a tumor organoid xenograft, we erased sentence: “Until now, tumor organoid is currently most effective application for drug screening.” We also make the conclusion section to improve the completion of this manuscript.
Detailed concerns (examples)
The abstract does not well reflect the content and results of the review. It is much too superficial.
All abbreviations need the full term for explanation at first occurrence (e.g. line 32).
line 32: “... mutation of APC ...” should read “... mutation of the APC (adenomatous polyposis coli) gene...”.
line 39-40: missing citation number.
line 89: What is the meaning of this sentence?
We appreciated the reviewer’s comments. As reviewer’s comments, we added the explain full term of all the first abbreviation. We also added missing citation number and we erased the ambiguous sentence. We hope that the reviewer #2 is satisfied with our revised version of manuscript.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
I have no more comments
Author Response
Thanks for reviewing my manuscript.
Reviewer 2 Report
The author (only single author listed, therefore it is unclear why Dr. Cho always uses the pronoun “we”) responded to some of my concerns. However, he did not add any new information, which would for instance include a table providing an overview of the current advanced models. A major concern is that he did not improve the English language use as necessary. Therefore, the manuscript is clumsy and hard to read.
Just one example (there are many more!):
Line 63-65: “The cancer cells containing the stemness are grown with high efficiencies into self-organizing cancer phenotypic structures [22, 23]. They are usually recapitulate and propagate their corresponding tissues.“ These sentences are linguistically incorrect. A cancer cell cannot “contain” stemness. “... are grown ...” is not suitable. You may say: “Cancer stem cells can grow into self-organizing spheroids, reflecting some structural aspects of native cancer tissue.”
Author Response
Point-by-point response to the reviewers
We appreciate the reviewer #2 for their constructive comments for improvement of the manuscript. The revised manuscript is substantially improved by addressing reviewer’s comments. English of this manuscript have been improved by is CIMB English editing service. We hope that our revised manuscript is now suitable for publication in Current issues in molecular biology.
Reviewer’s comments
Reviewer #2.
The author (only single author listed, therefore it is unclear why Dr. Cho always uses the pronoun “we”) responded to some of my concerns. However, he did not add any new information, which would for instance include a table providing an overview of the current advanced models.
Response: I appreciate reviewer’s comment. In this manuscript and point-by-point response letter, I changed “we” to appropriate pronoun or words. And I added 3 figures related with current advanced models such as cancer cell lines, PDTOs, PDTX.
A major concern is that he did not improve the English language use as necessary. Therefore, the manuscript is clumsy and hard to read. Just one example (there are many more!):
Line 63-: “The cancer cells containing the stemness are grown with high efficiencies into selforganizing cancer phenotypic structures [22, 23]. They are usually recapitulate and propagate their corresponding tissues.“ These sentences are linguistically incorrect. A cancer cell
cannot “contain” stemness. “... are grown ...” is not suitable. You may say: “Cancer stem cells can grow into selforganizing spheroids, reflecting some structural aspects of native cancer tissue.”
Response: I appreciate reviewer’s comment. Following your comments about English problems, English problems of this manuscript have been improved by CIMB English editing service.
