Bazedoxifene as a Potential Cancer Therapeutic Agent Targeting IL-6/GP130 Signaling

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The review, "Bazedoxifene as a Potential Cancer Therapeutic Agent," is precise and explores repurposing the FDA-approved drug for postmenopausal osteoporosis as an anticancer agent. The article is well-written, and I have a few suggestions-

1. Enhance Figure 1 by including a more detailed depiction of the molecular mechanisms underlying BZA's antitumor action.

2. In Tables 2 and 3, add information on ongoing clinical trials and their status for these cancer types.

3. The title for section 5.3, "Ovarian cancer," is the same as section 5.2. It likely needs correction to "Other Cancer Types."

4. The limitations of BZA are missing in this review. The author should add this section before the conclusion and future directions.

Author Response

Comment 1. Enhance Figure 1 by including a more detailed depiction of the molecular mechanisms underlying BZA's antitumor action.

Response 1: Thank you for your suggestions. We have revised Figure 1B to provide more details about the downstream pathways of IL-6/GP130 signaling. (page 3, line 122)

Comment 2. In Tables 2 and 3, add information on ongoing clinical trials and their status for these cancer types.

Response 2: Thank you for your suggestions. We have added an additional paragraph and table to summarize the completed and ongoing clinical trials investigating BZA as an anti-tumor agent. (page8-10, line 279-302)

Comment 3. The title for section 5.3, "Ovarian cancer," is the same as section 5.2. It likely needs correction to "Other Cancer Types."

Response 3: Thanks for pointing this out, we have changed the title as you mentioned (page 8, line 250).

Comment 4. The limitations of BZA are missing in this review. The author should add this section before the conclusion and future directions.

Response 4: Thank you for your suggestions. We add a paragraph on the limitation of BZA as anti-tumor agent (page 10, line 303-318).

Reviewer 2 Report

Comments and Suggestions for Authors

Authors Shi et al. of the manuscript Bazedoxifene as a Potential Cancer Therapeutic Agent describe the mechanism of action of this third-generation selective estrogen receptor modulator (SERM) as a potential antitumor drug, mainly in gynecological malignancies. The manuscript is written clearly and matter-of-factly. Next, I attach several suggestions for improving the quality and clarity of this article.

1. The article primarily describes the involvement of the IL-6/GP130 signaling pathway in cancer and its possible modulation. For this reason, it would be appropriate to modify the title to specify the content of the article by means of a description of the mechanism of action.

2. In Table 1, it is necessary to provide citations to confirm the statements and statistics presented in it.

3. It is advisable to add several pictures for a better understanding of the text. For example about the effect on individual types of tumor cells and more complex molecular mechanisms (similar to Table 3).

4. It is appropriate to add a section on the actual and potential side effects of BZA in antitumor induction and in the inductions in which it is currently used.

Comments on the Quality of English Language

I recommend publishing after minor revisions.

Author Response

Comment 1. The article primarily describes the involvement of the IL-6/GP130 signaling pathway in cancer and its possible modulation. For this reason, it would be appropriate to modify the title to specify the content of the article by means of a description of the mechanism of action.

Response 1: Thanks for pointing this out, we have modified the title as “Bazedoxifene as a Potential Cancer Therapeutic Agent Targeting IL-6/GP130 Signaling”. (page 1, line 2-3)

Comment 2. In Table 1, it is necessary to provide citations to confirm the statements and statistics presented in it.

Response 2: Thanks for your comments, we have added the citation for this table (page 5, line 171).

Comment 3. It is advisable to add several pictures for a better understanding of the text. For example about the effect on individual types of tumor cells and more complex molecular mechanisms (similar to Table 3).

Response 3: Thank you for your suggestions. We have created a new image to illustrate the inhibition of BZA on individual tumor types (page 4, line 133). For the mechanism, we revised Figure 1B to provide more details about the downstream pathways of IL-6/GP130 signaling (page 3, line 122).

Comment 4. It is appropriate to add a section on the actual and potential side effects of BZA in antitumor induction and in the inductions in which it is currently used.

Response 4: Thank you for your suggestions. We add a paragraph on the limitation of BZA as anti-tumor agent (page 10, line 303-318).