New Achievements for the Treatment of Triple-Negative Breast Cancer
, Domenico Iacopetta 2, Jessica Ceramella 2,*, Annaluisa Mariconda 3, Camillo Rosano 4, Domenica Scumaci 5, Carmela Saturnino 3, Pasquale Longo 6 and Maria Stefania Sinicropi 2
Round 1
Reviewer 1 Report
Ceramella and co-workers summarized the recent advances in the novel therapies used for the treatment of TNBC, including nutraceuticals and repositioning drugs. It is important to timely update the most rescent achievements in TNBC treatment. This review need to address the following issues before I can recommend its publication:
1. The title is no appropriate, "The New Challenges for the Treatment of Triple-Negative Breast Cancer", the authors did not spend much space to discuss about the challenges in the field of TNBC treatment, but mainly focused on introducing the recent advance. Therefore, "challenges" better change to "approaches" or "achievements";
2. Some of the paragraphs are too long, not easy to read. please seperate the long paragraphs for reader friendly;
3. Some importance examples of metal complex based approaches are missing. Especially, platinum (IV) prodrugs have been shown to exhibit high potential for TNBC treatment. Chem. Commun., 2018, 54, 11717; Angew. Chem. Int. Ed. 2020, 59, 23313; other examples of metal complex for TNBC treatment: Angew. Chem. Int. Ed. 2022, 61, e202115247.
Author Response
The authors replies to the reviewer 1 comments are in the attached pdf file.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Alessia Catalano et al reviewed the new Challenges for the Treatment of Triple-Negative Breast Cancer
1) The rationale of why the authors came up with this review.
2) What is the information that is not exactly available that motivated the authors to come up with this information. What are the current caveats and how do the authors highlight the current research in answering them? If not they need to address in future directions.
3) The underlying message here is that more precision and individualized approaches need to be tested in well designed clinical trials – a challenge, but I would be interested in their perspective of how this might be done.
4) This reviewer personally misses a graphical abstract or a workflow scheme summarizing the authors findings in a snapshot
5) As is now well known, tumors grow and evolve through a constant crosstalk with the surrounding microenvironment, and emerging evidence indicates that angiogenesis and immunosuppression frequently occur simultaneously in response to this crosstalk. Accordingly, strategies combining anti-angiogenic therapy and immunotherapy seem to have the potential to tip the balance of the tumor microenvironment and improve treatment response (please comment and expand)
6) In the frame of point 5) thinking, this reviewer personally misses some insights regarding the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) is a well-established inhibitory immune checkpoint axis in triple-negative breast cancer (TNBC). Growing evidence indicates that tumoral PD-L1 can lead to TNBC development. Although conventional immune checkpoint inhibitors have improved TNBC patients’ prognosis, their effect is mainly focused on improving anti-tumoral immune responses without substantially regulating oncogenic signaling pathways in tumoral cells. Moreover, the conventional immune checkpoint inhibitors cannot impede the de novo expression of oncoproteins, like PD-L1, in tumoral cells. Accumulating evidence has indicated that the restoration of specific microRNAs (miRs) can downregulate tumoral PD-L1 and inhibit TNBC development. Since miRs can target multiple mRNAs, miR-based gene therapy can be an appealing approach to inhibit the de novo expression of oncoproteins, like PD-L1, restore anti-tumoral immune responses, and regulate various intracellular singling pathways in TNBC (please refer to PMID: 34440380) and expand
7) The authors need to highlight what new information the review is providing to enhance the research in progress.
Author Response
The authors replies to the reviewer 2 comments are in the attached pdf file.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The authors have addressed all the issues, I recommend publication in its present form.
Reviewer 2 Report
The authors have clarified several of the questions I raised in my previous review. Most of the major problems have been addressed by this revision.
