Exploiting Integrin-αVβ3 to Enhance Radiotherapy Efficacy in Medulloblastoma via Ferroptosis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

I red with interest your paper entitled "Exploiting Integrin-αVβ3 to enhance radiotherapy efficacy in 2 medulloblastoma via ferroptosis". Your study present a certain degree of novelty, but it can be improved before publication.

Thisr reviewer has some suggestions to strenghten your conclusions.

Major comments

1. Lines: 209-213: your hypothesis of a synergy between beta3 depletion and GPX4/xCT inhibition should be also investigated depleting the genes of interests (by specific siRNAs experiments for example). Chemical inhibition is not sufficient to claim conclusions

2. Paragraph 3.2: to affirm that beta3 depletion does not affect GPX4 protein stability a set of experiments by inhibiting the proteasome machinery (time course with MG132) should be also performed

Minor

1. Lines 246-247: please, change "GPX4 gene expression" with "GPX4 mRNA levels"

2. Line 297: this reviewer believes that a verb is missing ("We next..?...cilengitide"

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Gotorbe and colleagues explored the potential role of Integrin-αVβ3 in ferroptosis in medulloblastoma. The paper is well written and presents a good molecular characterisation of Integrin-αVβ3 in some aspects of radiation-induced ferroptosis, however, a few points should be implemented.

 

-The authors should show the symbol representing biological replica in all the graphs.

 

-Figure 3C: The authors should present quantification of at least 3 biological replicas.

 

-The authors should show the effect of cilengitide on integrin-αvβ3 expression.

  Minor points:

-line 188: Authors state “at every investigated dose” but higher concentrations are not significantly changing. Please adjust the text.

 

 

-line 297: it looks like one word is missing between “We next” and “cilengitide”

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors, I have just very few modifications to request. Please, add a sentence indicating that also proteasome degradation was investigated to exclude beta3-dependent regulation of GPX4 stability (line 254). The experiment may be included as a supplemental data or indicated as "not shown". Further, explain in the text, as you did to this reviewer, why genetic ablation of xCT/GPX4 is not possible, as this issue is unknown to non expert readers in the field. 

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Round 3

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

I have no further issue to request. To this reviewer, this paper is now suitable for publication in Curr Oncol. With my best wishes for your future work.