Therapeutic Potential and Challenges of Pioglitazone in Cancer Treatment

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript describes the application of pioglitazone in cancer treatment. The topic of review is actual, this drug is commonly used for treatment of patients with cancer. The authors given the deep insight in the topic. The described both mechanisms of action as well as different examples of clinical use of pioglitazone. The article is very well discussed using 128 references. As for English, I am not native speaker, for me English is acceptable. Everything is clear to read and understand. The article will be interesting for wide range of sciencists - both molecular biologists and clinical scientists. I think article can be published after minor corrections.

I have minor remarks:

One figure for review is not enough. Please add additional 3-4 figures illustrating effects of pioglitazone.

Also, please add the table with the data on clinical trials with this drug.

Author Response

Thank you for your review. According to your comments we made the corrections below:

 

We have included figures 2, 3 and 4 which illustrate the effect and mechanism of pioglitazone on different systems.

We have added supplementary table 2 with data regarding pioglitazone from clinical trials.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Author,

I have read the paper titled "Therapeutic potential and challenges of pioglitazone in cancer treatment.” As you stated, the review summarizes clinical data, epidemiological studies, pharmacokinetics, therapeutic potential, and regulatory recommendations to evaluate the risk-benefit ratio of the clinical use of pioglitazone, focusing on cancer treatment. You conclude that pioglitazone possesses antineoplastic agent properties. Although in vitro studies have been carried out with positive results, the adverse events presented indicate that additional studies are required to fully assess the risk-to-benefit ratio in an evidence-based manner.

The paper is well organized and written, with interesting information presented throughout. However, a significant drawback is that most of the findings are based on in vitro studies. This limits our ability to infer therapeutic potential, as conclusions from in vitro research or animal models may not translate effectively to humans. Additionally, the manuscript lacks a thorough discussion regarding the number of subjects involved in each study, their sex, the duration of treatment, and the dosage used.

In its current form, the manuscript cannot be accepted for publication. You must address the following comments before publication can be considered.

1.       More clinical trials should be included to provide robust evidence of the therapeutic potential of pioglitazone in cancer treatment. 

2.       Each study must include information about the number of subjects involved, their sex, the duration of treatment, and the dosage used. 

3.       To improve the discussion section, which currently contains two paragraphs. One paragraph discusses metformin instead of pioglitazone, which needs to be addressed.

4.       The conclusions leave readers in the same state as when they began reading the manuscript. The statement that "pioglitazone possesses antineoplastic properties and although in vitro studies have shown positive results, the adverse events reported indicate that additional studies are necessary to assess the risk-to-benefit ratio in an evidence-based manner fully" is something that those interested in this manuscript are likely already aware of. What we want to know is the specifics of the "additional studies conducted to assess the risk-to-benefit ratio in an evidence-based manner."

5.       I highly recommend adding more references from the last five years to emphasize the current interest in the topic reviewed. Less than 40 % of the listed references are from the previous 5 years.

Author Response

Thank you for your review. According to your comments we made the corrections below:

 

1. We have included a table with pioglitazone data from clinical trials.
2. We have added information about the number of participants, their sex, the duration of treatment, and the dosage used, as requested.
3. The discussion section has been revised. The 2^nd paragraph which referred to metformin has been omitted and replaced with more details regarding the time- and dose-dependent relationship of pioglitazone.
4. The conclusion has been revised. Evidence from the discussion section helps reach a clear conclusion.
5. We have added references from the latest clinical trials and cohort studies. Also, we rearranged their order.

Reviewer 3 Report

Comments and Suggestions for Authors The study entitled: Therapeutic potential and challenges of pioglitazone in cancer treatment is sound and will be valuable for AS-Journal readers. The study is a well written review about pioglitazone and its valuable potential in cancer treatment. The strong point of study is high quality background and appropriate references choice. On the other hand, there are a few minor remarks to reconsideration - please refer to below list:  1. ,,5-{4-[2-(5-Éthyl-2-pyridinyl)éthoxy]benzyl}-1,3-thiazolidine-2,4-dione'' - please adjust to English language. 
2. Please correct ordering of references - the number 33 is missing (should be in text between 31,32 and 34). 3. Please correct the Table 1 according to 1st column - a few "Mechanism" are not conjuncted with proper "Process".  4. Cancer type in last line of Table 1 is missing.  5. The text: ,,Acknowledgments: Figure 1 was created using ACD/ChemSketch, version 2021.2.0 (Advanced 448 Chemistry Development, Inc., Canada; www.acdlabs.com, 2022). Figure 2 was created using 449 https://biorender.com. URL accessed on 25 October 2024." should be divided into parts and added to appropriate figures footer (names). 6. I am not fully sure, if the references are cited properly (according to journals abbreviations and Applied Sciences Journal Guidelines etc.) - please correct if applicable. On the other hand, the references are appropriate to manuscript theme.  7. ,,IU-PAC'' please correct for IUPAC and add full name.  8. Please change ,,pioglitazone HCl" for ,,pioglitazone hydrochloride". In next sentence you may used abbreviation of API. 9. The tables and figures (except points 3-5) are appropriate and well designed. 

 

10. Discussion is efficient and the study has been compared with other studies. 

9-PACiii

Author Response

Thank you for your review. According to your comments we made the corrections below:

 

1. We have adjusted the chemical name to English.
2. Reference 33 is added in the text, which was accidentally omitted.
3. We have corrected column 1 of table 1, with more accurate processes.
4. We have added the cancer type that was missing on the last line of table 1.
5. Acknowledgments are stated in footers, as requested.
6. The references are in concordance with the journal’s instructions.
7. We provide the abbreviation of IUPAC.
8. Pioglitazone “HCl” has been corrected to “hydrochloride”, as requested.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Editor,

I have read an improved version of the paper titled "Therapeutic potential and challenges of pioglitazone in cancer treatment.” I appreciate the authors' effort to address the previous comments. The partially addressed comment pertains to the number of references from the last five years. Although the authors increased the number of references from 128 to 160, many are older than five years. I highly recommend retaining references from the last five years and older that significantly contribute to the topic reviewed.

The manuscript can be accepted for publication once the authors have addressed the comments regarding the references.

Comments on the Quality of English Language

The quality of the English language is sufficient for understanding the manuscript. However, it could be enhanced to convey the general ideas more clearly.

Author Response

Thank you for your comment. We have revised the manuscript and replaced old references with recent ones from the last 5 years. We retained a small number of older references owing to the distinctive nature of the studies. Changes are in gray color.