Peptidergic G-Protein-Coupled Receptor Signaling Systems in Cancer: Examination of Receptor Structure and Signaling to Foster Innovative Pharmacological Solutions

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript describes the GPCR structure and the mechanisms these proteins use to induce carcinogenesis. The manuscript is clear and well-written, but it should be better balanced. The authors deepen the role and, mainly, the structure of these receptors but the paragraphs describing the use of peptidergic GPCR antagonists and agonists as tumor drugs are limited and scant information, despite the manuscript title: “Peptidergic GPCRs Signaling Systems and Cancer: Into New Pharmacological Approaches”.

The authors assert that many compounds are used to treat other pathologies. They could describe how these drugs work and search for information about a correlation between the incidence of cancers in patients treated with these drugs (for other pathologies, not for cancer).

Comments on the Quality of English Language

Minor editing of English language required.

Author Response

Referee   #1

This manuscript describes the GPCR structure and the mechanisms these proteins use to induce carcinogenesis. The manuscript is clear and well-written, but it should be better balanced. The authors deepen the role and, mainly, the structure of these receptors, but the paragraphs describing the use of peptidergic GPCR antagonists and agonists as tumor drugs are limited and scant information, despite the manuscript title: “Peptidergic GPCRs Signaling Systems and Cancer: Into New Pharmacological Approaches”.

The authors assert that many compounds are used to treat other pathologies. They could describe how these drugs work and search for information about a correlation between the incidence of cancers in patients treated with these drugs (for other pathologies, not for cancer).

Minor editing of English language required.

 We are very thankful for the comments. This manuscript focuses on a detailed description of the structures of the GPCR receptors and their signaling pathways. This knowledge is essential for designing new pharmacological tools to fight some tumors dependent on receptor malfunction. Consequently, we have modified the title of the review to highlight the relevance of structural analysis and main signaling pathways, as follows:

“Peptidergic GPCR Signaling Systems in Cancer: Examination of Receptor Structure and Signaling to Foster Innovative Pharmacological Solutions.”

Also, in the Conclusions and Future Directions section, we have pointed out the use of some drugs aimed at other therapeutic applications rather than cancer (For example, aprepitant, an NK-1R antagonist, or “gepants” for migraine, etc.). (Lines 637-643).

The text has been thoroughly reviewed for errors.

See modifications in red.

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

 

 

The manuscript entitled” Peptidergic GPCRs Signaling Systems and Cancer: Into New Pharmacological Approaches” by Rodriguez and  Coveñas is a timely review that explains the topic well. This well-written and insightful review highlights the significant role of peptidergic GPCR systems in cellular regulation and survival. The authors have clearly articulated how dysfunction in these systems, whether through overactivation or failure, can lead to severe cellular disturbances, contributing to tumor formation and progression.

Author Response

Referee # 2

The manuscript entitled” Peptidergic GPCRs Signaling Systems and Cancer: Into New Pharmacological Approaches” by Rodriguez and Coveñas is a timely review that explains the topic well. This well-written and insightful review highlights the significant role of peptidergic GPCR systems in cellular regulation and survival. The authors have clearly articulated how dysfunction in these systems, whether through overactivation or failure, can lead to severe cellular disturbances, contributing to tumor formation and progression.

Thank you for your positive comments.

Some modifications have been introduced in the text to clarify sentences or correct misspellings (in red).

Reviewer 3 Report

Comments and Suggestions for Authors

Abstract: Line 14, 15 needs modification. These lines are confusing.

Figure descriptions are too long and there is no need for references in them.

Line-436: No need for a single line paragraph, merge with the paragraph below.

Line: 510-511 needs revision. Its confusing.

 

 

Comments on the Quality of English Language

Minor corrections are needed

Author Response

Referee # 3

Thank you very much for the comments and suggestions for improving the manuscript. We have revised the text accordingly and made some corrections appearing in red in the manuscript.

Abstract: Line 14, 15 needs modification. These lines are confusing.

            The sentence has been checked and rephrased (lines 15-17)

Figure descriptions are too long and there is no need for references in them.

The description within the captions of the figures is necessary so that every figure is self-explanatory and contains sufficient information, even though it may appear repeated in different figures (abbreviations, references, and descriptions concerning elements of the figure).

Line-436: No need for a single-line paragraph; merge with the paragraph below.

This has been corrected (lines 436-437)

Line: 510-511 needs revision. It's confusing.

These lines have been reviewed and rephased to make it more clear (lines 510-511)

Minor corrections are needed

The text has been thoroughly reviewed for minor corrections.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors produced all the modifications useful in removing criticisms of the manuscript.