Potential of Exosomes as Therapeutics and Therapy Targets in Cancer Patients

Round 1

Reviewer 1 Report

The review is very well organized and written. I have only two points to consider:

1. The issue of a drawback of using exosomes as a treatment when they contain thousands of unknown molecules should be elaborated in the discussion. This fact may be harmful due to the unknown possible effects of these exosomes upon transferring a large amount of them into the human body.

2. The paragraph starting at line 134: it should be added that exosomes are also delivered back from the surrounding cells into the tumor cells.

Author Response

The reviewer’s comments are numbered and in regular font, while my reply is in italic. Modifications made in the revised manuscript are highlighted in red.

I would like to thank the reviewer for her/his time and effort to provide the review. I have carefully and substantially revised the manuscript according to the suggestions provided.

Reviewer 1

1. The issue of a drawback of using exosomes as a treatment when they contain thousands of unknown molecules should be elaborated in the discussion. This fact may be harmful due to the unknown possible effects of these exosomes upon transferring a large amount of them into the human body.

This is a very important point. Now, I elaborated it in the discussion and conclusion on page 11.

2. The paragraph starting at line 134: it should be added that exosomes are also delivered back from the surrounding cells into the tumor cells.

I added “that exosomes are also delivered back from the surrounding cells into the tumor cells to page 4 (lines 155-156).

Reviewer 2 Report

The manuscript entitled, “Potential of Exosomes as therapeutic and therapy targets in cancer patients” is interesting. However, there are a few comments that need to be discussed.

 Major comments:

1.      While the review manuscript covers the recent updates in the field, most of the studies are superficially discussed. For example, the detailed mechanisms by which drug-loaded exosomes induce greater antitumor and cytotoxicity compared to drug alone is not discussed.  

2.      From the readers’ perspective, it is important to highlight the overall summary of experimental studies utilizing exosomes as therapeutic agents and therapy targets in a tabulated form.    

Minor comments:

1.   The authors should increase the reference base for several common statements highlighted in the “Introduction” section. There is only 1 reference for such an important topic.

Author Response

The reviewer’s comments are numbered and in regular font, while my reply is in italic. Modifications made in the revised manuscript are highlighted in red.

I would like to thank the reviewer for her/his time and effort to provide the review. I have carefully and substantially revised the manuscript according to the suggestions provided.

Reviewer 2

1. While the review manuscript covers the recent updates in the field, most of the studies are superficially discussed. For example, the detailed mechanisms by which drug-loaded exosomes induce greater antitumor and cytotoxicity compared to drug alone is not discussed.

A new paragraph which compares the delivery of drug-loaded exosomes with free drugs was added to page 7 (6. Drug-loaded exosomes vs. free drugs in cancer treatment).

2. From the readers’ perspective, it is important to highlight the overall summary of experimental studies utilizing exosomes as therapeutic agents and therapy targets in a tabulated form.

Table 1 (page 9) and Table 2 (page 10) were added and mentioned in the text (pages 7 and 9).

Minor comments:

1. The authors should increase the reference base for several common statements highlighted in the “Introduction” section. There is only 1 reference for such an important topic.

References 2, 5, 8,12,13, 23, 26 were added to pages1-3.

Reviewer 3 Report

The review article by Schwarzenbach discusses the issue of chemotherapy resistance and tumor relapse in cancer patients, highlighting exosomes as crucial mediators of cell-to-cell communication involved in cancer progression and therapy resistance. Exosomes have the potential to serve as efficient drug delivery systems, advancing targeted therapy and enhancing the effectiveness of anti-cancer medications. The review provides an overview of exosomes as therapeutic agents and targeted molecules in cancer treatment, while also addressing challenges in preparing and loading exosomes with drugs and delivering them to tumor cells for effective therapy.

The article is generally of good quality and well-written. I would suggest improving the following minor points:

·         Line 39-42. A reference/s is needed at the end of this statement.

·         Line 130-133. It would be interesting to further expand upon this paragraph. It may be worth adding more specific examples of the role of exosomes in circulation.

·         Line 150-153. It would be interesting to cite a few more examples of miRNAs in addition to miR-155.

·         I suggest changing the style of the text box in Figure 1. The 3D effect on the box is inappropriate. Enhance the quality of the arrows in the right section of the figure. Additionally, I recommend rotating the words "Integrin" and "Tetraspanins" for better readability.

N/A

Author Response

The reviewer’s comments are numbered and in regular font, while my reply is in italic. Modifications made in the revised manuscript are highlighted in red.

I would like to thank the reviewer for her/his time and effort to provide the review. I have carefully and substantially revised the manuscript according to the suggestions provided.

Reviewer 3

1. Line 39-42. A reference/s is needed at the end of this statement.

Reference 8 was added to page 1.

2. Line 130-133. It would be interesting to further expand upon this paragraph. It may be worth adding more specific examples of the role of exosomes in circulation.

Now, I added some sentences to this paragraph to describe more specifically the exosomes in the circulation (page 4, lines 131-148).

3. Line 150-153. It would be interesting to cite a few more examples of miRNAs in addition to miR-155.

Now, I added miR-23a, miR-200 and miR-146a to the paragraph (page 4, lines 166-175).

4. I suggest changing the style of the text box in Figure 1. The 3D effect on the box is inappropriate. Enhance the quality of the arrows in the right section of the figure. Additionally, I recommend rotating the words "Integrin" and "Tetraspanins" for better readability.

I removed the 3D effect of the box, enhanced the arrows in the right section and rotated the words "Integrin" and "Tetraspanins" (page 3).

Round 2

Reviewer 2 Report

The authors have satisfactorily addressed my comments. I have no further comments.