Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review
Round 1
Reviewer 1 Report
Comments:
1) The abstract states that “metformin is the first-line drug for the treatment of type 2 diabetes”. This is partially correct. Current guidelines did not propose it as first-line drug for patients with high cardiovascular risk, a current cardiovascular disease or renal failure. Later in this section, it is stated that metformin has “hypoglycemic” effects. I suggest using “anti-hyperglycemic effects or glucose-lowering effects” instead. Also correct this asseveration along the manuscript.
2) Please, avoid terms as “diabetic patients”. Use “patients with diabetes” instead.
3) Line 42-44 mention “diabetic patients” in reiterative form.
4) In the Figure 2 and 3, specify the meaning of abbreviations. The figure should be understood without searching the meaning of abbreviations into text.
5) What did you mean with low doses of metformin in line 133? An issue in some experiments related with metformin is that doses employed in animals are much bigger than those employed in humans. Please add this to your review.
6) It could be interesting adding a table that summarize the effects of metformin in the hematological malignancies described. I suggest adding metformin doses employed in each study and the time of its use. Another option is describing these into the manuscript.
7) I suggest adding bullets (or subsections like 3.1, 3.2, etc) in the section relating to other cancer-related signaling pathways (lines 151-168). This could improve the reding of this section. In this section, please clarify how cholesterol biosynthesis inhibition is also involved as anti-cancer mechanism.
8) Subheading 2.2.2 is confusing. What do you mean with activation of AMPK-independent cells?
9) Suppress the comma after (4E-BP1) in line 278. Add an “I” in the word “In” at the beginning of line 281.
10) What does “metformin deficiency” refers to in line 355?
11) Correct the word “gammopathy of” in line 390
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
In this review article, Authors. Summarized various mechanisms of metformin for anti-cancer, which provide insight into the Metformin in the treatment of Hematological Malignancy. This review paper was written while approaching the regulatory mechanisms for the adjuvant cancer therapy. However, there is no special innovation in the manuscript, and I doubt that these results provide an advancement of the current knowledge. Therefore, if the following comments are revised, it is likely to be possible to re-evaluate the manuscript.
It is very similar to an article titled "Metformin - its anti-cancer effects in hematologic malignancies" and it is modeled from this article (doi: 10.4081/oncol.2021.514).
(Major Comments)
1. It is suggested to revise the title of the manuscript. This title is repeated, and an article with the same title has been published.
2. First of all, the content of the introduction is too distracting and there is no exact suggestion on what to explain in this article.
3. The text explained in the title Metformin mechanism of action has nothing to do with the heading.
4. In this manuscript, Authors claim they presented a quite review on the role of Metformin in Hematological Malignancy. While I appreciate the effort put to this manuscript, I am not convinced this would interest the authors of Archives of drug Research. There are so many activities of metformin listed in this article, and they seem unthreaded beads. Furthermore, I am not sure how this manuscript differs to the recent review article titled as "Metformin - its anti-cancer effects in hematologic malignancies: a review" written by the Monika Podhorecka.(doi: 10.4081/oncol.2021.514).
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
The manuscript was very well reviewed and improved and it can be accepted for publication.
Author Response
Dear Reviewer:
Thanks very much for your kind work and consideration on the publication of our manuscript (ID: biomolecules-2042320). On behalf of my co-authors, I would like to express our great appreciation to you. Thank you very much for your comments, the final version of this manuscript was completed under your experienced guide. Without this revision step, we would not have been able to depict the link between metformin and hematological malignancy in the manuscript. The process of learning from this writing also laid the foundation for further knowledge about metformin and hematological malignancy in our lab.
Once again, thank you very much for your comments and suggestions.
