Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

In the manuscript, the structural details and inhibitor binding of the clinically relevant ABC transporters were elucidated. Besides, mechanistic overview and novel therapeutic strategics of ABC transporters were provided. I recommend it for publication after minor revisions.

1. In the manuscript, one of “.”in“These authors are contributed equally. .” should be removed. The Figure 1 should be adjusted. Need to check whether the article space is used correctly. Please carefully review the entire manuscript and check the gramma and format.

2. Please note that ROS requires the full name when it first appears. Please carefully review the entire manuscript and find out similar issues.

3. There is no literature references to support the advantages and disadvantages of RNA interference therapy. Please cite examples before drawing conclusions. Please carefully review the entire manuscript and find out other places without accurate citations.

4. It may be necessary to add a map of the corresponding targets of drug therapy to make it more convenient for people to understand the article. Please carefully review the entire manuscript.

5. References should be listed out in Table 1, Table 3.

 

 

Author Response

Reviewer 1

In the manuscript, the structural details and inhibitor binding of the clinically relevant ABC transporters were elucidated. Besides, mechanistic overview and novel therapeutic strategics of ABC transporters were provided. I recommend it for publication after minor revisions.

1. In the manuscript, one of “.”in“These authors are contributed equally. .” should be removed. The Figure 1 should be adjusted.Need to check whether the article space is used correctly. Please carefully review the entire manuscript and check the grammar and format.

Thank you to the reviewers for their comments. We removed “These authors contributed equally” from the manuscript and rearranged Figure 1. We corrected formatting and English grammatical errors throughout the manuscript and highlighted the changes in yellow.

2. Please note that ROS requires the full name when it first appears. Please carefully review the entire manuscript and find out similar issues.

ROS was expanded to include reactive oxygen species, which were meticulously checked for other influencing factors in the manuscript.

3. There is no literature references to support the advantages and disadvantages of RNA interference therapy. Please cite examples before drawing conclusions. Please carefully review the entire manuscript and find out other places without accurate citations.

We cited PMID: 19284376, and we already cited relevant citations for this topic in the manuscript, i.e., reference # 170-173.

4. It may be necessary to add a map of the corresponding targets of drug therapy to make it more convenient for people to understand the article. Please carefully review the entire manuscript.

Thanks to the reviewer for the comment. We went through the manuscript and believe that the included tables and figures sufficiently explain the corresponding targets of drug therapy, providing enough information for readers to understand the manuscript.

5. References should be listed out in Table 1, Table 3.

The references are cited in Tables 1 and 3 and highlighted in yellow in the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

The review addresses a very important and actual problem of multidrug resistance caused by multidrug transporters. Though numerous reviews covered the structure of ABC transporters and various therapeutical approach to the multidrug resistance, this concise review addressing both the structure of transporters, their role in multidrug resistance and summary of contemporary therapeutic ideas may be useful for researchers and practitians.

Remarks:

Page 1: „ in both sexes and ages”, unclear, please correct

Page 4: It could be mentioned that the ABCB1 gene product was first referred to as glycoprotein P. This name is mentioned later on but it is not clear from the text that glycoprotein P is ABCB1. Please introduce the acronym ”P-gp” later on.

Page 4: “called P glycoproteins”, should be “called P glycoprotein”

Page 4: When introducing the ABCC family, its characteristic structural feature (the presence of the TMD0 domain) can be mentioned

Table 1: “amnio acid“, please change to “aminoacid”

„of glutathione conjugate”, better: „of glutathione conjugates”

 

Table2. ABCC1 transports also glutathione S-conjugates and GSSG

 

Author Response

Reviewer 2

The review addresses a very important and actual problem of multidrug resistance caused by multidrug transporters. Though numerous reviews covered the structure of ABC transporters and various therapeutical approach to the multidrug resistance, this concise review addressing both the structure of transporters, their role in multidrug resistance and summary of contemporary therapeutic ideas may be useful for researchers and practitians.

Remarks:

Page 1: „ in both sexes and ages”, unclear, please correct

Thank you to the reviewer for the comments. Changed as follows: across both sexes and all age groups.

Page 4: It could be mentioned that the ABCB1 gene product was first referred to as glycoprotein P. This name is mentioned later on but it is not clear from the text that glycoprotein P is ABCB1. Please introduce the acronym ”P-gp” later on.

We corrected and highlighted in yellow in the manuscript.

Page 4: “called P glycoproteins”, should be “called P glycoprotein”

Corrected and highlighted in yellow in the manuscript.

Page 4: When introducing the ABCC family, its characteristic structural feature (the presence of the TMD0 domain) can be mentioned

Thank you, and this is now incorporated under the ABCC section. Highlighted in yellow.

Table 1: “amnio acid “, please change to “aminoacid”

„of glutathione conjugate”, better: „of glutathione conjugates”

Corrected all the above in Table 1.

Table2. ABCC1 transports also glutathione S-conjugates and GSSG

Included ‘glutathione S-conjugates and GSSG” in Table 2.