Molecular and Cellular Mechanisms of Static and Repetitive Magnetic Stimulation in Cancer Therapy: A Scoping Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript provides a comprehensive and up-to-date review of preclinical research on the use of static magnetic stimulation (sMS) and repetitive magnetic stimulation (rMS) in cancer therapy. The work's topic is interdisciplinary and compelling, combining elements of molecular biology, biophysics, and experimental oncology. The authors attempt to organize the scattered literature, which in itself is valuable for this emerging field of research. The work is clearly identified as a scoping review, and in most cases, the authors maintain the methodological consistency appropriate for this type of work.

Strengths of the paper:

1. The appropriate choice of methodology. The scoping review format is suitable for a heterogeneous and still early research area.
2. The extensive and well-documented literature review, encompassing both in vitro and in vivo models, is comprehensive and consistently maintained throughout the manuscript.
   The clear distinction between sMS and rMS is consistently maintained throughout the manuscript.
3. The highly detailed tables detailing stimulation parameters, biological models, and endpoints significantly enhance the paper's usefulness as a reference.
4. The careful formulation of conclusions with respect to potential clinical applications.
   
   

Major concerns:

1. Limited mechanistic integration. Although the title suggests an analysis of "molecular and cellular mechanisms," much of the manuscript is descriptive, and the proposed mechanisms are often inferred only indirectly from the research findings. A clear distinction is lacking between primary biophysical effects of magnetic fields, secondary cellular responses (ROS, Ca²⁺, autophagy), and downstream molecular consequences (signaling pathways). It would be advisable to strengthen the discussion section with a more synthetic approach to the mechanisms.
2. Insufficient exposure of conflicting results (especially for sMS). Although the review reports several studies demonstrating antitumoral effects of sMS, the Results section also includes neutral, protective, and potentially pro-tumorigenic outcomes depending on experimental context and stimulation parameters (e.g., lines ~299–305, ~355–357, ~379–380). These findings indicate that sMS can elicit biologically divergent responses. In the Discussion (approximately lines ~380–433), these contradictory results are not sufficiently emphasized, and sMS is predominantly presented as a promising antitumoral adjunct. As a result, the overall narrative may appear more uniformly positive than the data fully support. Given the preclinical nature of the evidence and the substantial heterogeneity of stimulation protocols, a more balanced interpretation is warranted. Strengthening the Discussion to explicitly address the bidirectional and context-dependent effects of sMS, and reflecting this more clearly in the Conclusions, would improve the scientific rigor of the manuscript and reduce the risk of overinterpretation.
3. Limited translational value, no clear indication of barriers. Although the authors rightly emphasize the preclinical nature of the data, they fail to explicitly discuss the lack of protocol standardization, difficulties in scaling magnetic exposure, and potential biological risks associated with prolonged or suboptimal stimulation.

Minor concerns:

1. In the Discussion section, several passages are repetitive and overly descriptive, reiterating results already presented in detail in the Results section rather than providing higher-level synthesis and interpretation. In particular, the discussion of frequency-dependent effects of repetitive magnetic stimulation (rMS) on cell proliferation and signaling pathways (approximately lines 399–410) essentially restates findings previously described in the Results. Similarly, the detailed recounting of the Jo et al. studies and Wnt/β-catenin pathway modulation (approximately lines 411–433) repeats the experimental details, including specific assays and molecular targets, rather than focusing on their broader biological implications. These repetitions diminish the Discussion's conceptual clarity and obscure opportunities for integrative interpretation across studies. Condensing these sections and shifting the emphasis toward comparative analysis, mechanistic synthesis, and identification of overarching patterns would significantly improve readability and strengthen the scientific contribution of the Discussion.

2. It is worth considering adding a diagram summarizing the proposed mechanisms of sMS and rMS.

3. Given the heterogeneity of responses to static and repetitive magnetic stimulation across tumor models, I wonder whether the authors could briefly comment on whether any potential molecular or cellular markers of response can be tentatively inferred from the reviewed studies. Even a short statement addressing possible candidate pathways, or explicitly noting that the current evidence is insufficient to identify such markers, would further strengthen the Discussion.
4. I recognize that this manuscript is a scoping review and that a quantitative synthesis is not required. However, I would be interested if the Authors could briefly comment in the Discussion on whether any qualitative or approximate quantitative trends (for example, related to stimulation intensity, frequency, or exposure duration) can be inferred from the available studies, or note that the current evidence does not allow such conclusions.

Comments on the Quality of English Language

While the English is generally clear, several sentences are overly long or awkwardly structured, particularly in the Introduction (e.g., lines ~45–52, ~73–81) and Discussion (e.g., lines ~399–406, ~411–418), and would benefit from stylistic simplification.

Author Response

Reviewer 1

Date of this review: 17 Jan 2026 15:22:13

Quality of English Language: The English could be improved to more clearly express the research.

Comments and Suggestions for Authors

This manuscript provides a comprehensive and up-to-date review of preclinical research on the use of static magnetic stimulation (sMS) and repetitive magnetic stimulation (rMS) in cancer therapy. The work's topic is interdisciplinary and compelling, combining elements of molecular biology, biophysics, and experimental oncology. The authors attempt to organize the scattered literature, which in itself is valuable for this emerging field of research. The work is clearly identified as a scoping review, and in most cases, the authors maintain the methodological consistency appropriate for this type of work.

Strengths of the paper:

1. The appropriate choice of methodology. The scoping review format is suitable for a heterogeneous and still early research area.
2. The extensive and well-documented literature review, encompassing both in vitro and in vivo models, is comprehensive and consistently maintained throughout the manuscript.
3. The clear distinction between sMS and rMS is consistently maintained throughout the manuscript.
4. The highly detailed tables detailing stimulation parameters, biological models, and endpoints significantly enhance the paper's usefulness as a reference.
5. The careful formulation of conclusions with respect to potential clinical applications.
   R: Dear reviewer, thank you for your comprehensive assessment of the manuscript. The responses to your inquiries are provided below.

Major concerns:

1. Limited mechanistic integration. Although the title suggests an analysis of "molecular and cellular mechanisms," much of the manuscript is descriptive, and the proposed mechanisms are often inferred only indirectly from the research findings. A clear distinction is lacking between primary biophysical effects of magnetic fields, secondary cellular responses (ROS, Ca²⁺, autophagy), and downstream molecular consequences (signaling pathways). It would be advisable to strengthen the discussion section with a more synthetic approach to the mechanisms.

R: This is an interesting point. The entire Discussion section has been restructured and rewritten with an emphasis on potential mechanisms of action. 

2. Insufficient exposure of conflicting results (especially for sMS). Although the review reports several studies demonstrating antitumoral effects of sMS, the Results section also includes neutral, protective, and potentially pro-tumorigenic outcomes depending on experimental context and stimulation parameters (e.g., lines ~299–305, ~355–357, ~379–380). These findings indicate that sMS can elicit biologically divergent responses. In the Discussion (approximately lines ~380–433), these contradictory results are not sufficiently emphasized, and sMS is predominantly presented as a promising antitumoral adjunct. As a result, the overall narrative may appear more uniformly positive than the data fully support. Given the preclinical nature of the evidence and the substantial heterogeneity of stimulation protocols, a more balanced interpretation is warranted. Strengthening the Discussion to explicitly address the bidirectional and context-dependent effects of sMS, and reflecting this more clearly in the Conclusions, would improve the scientific rigor of the manuscript and reduce the risk of overinterpretation.

R: These topics were adequately addressed in the Discussion section and highlighted in the Conclusion. In addition, the Discussion was subdivided into topics for a better understanding of the differences between the techniques, highlighting the conflicting results.

3. Limited translational value, no clear indication of barriers. Although the authors rightly emphasize the preclinical nature of the data, they fail to explicitly discuss the lack of protocol standardization, difficulties in scaling magnetic exposure, and potential biological risks associated with prolonged or suboptimal stimulation.

R: These topics were better addressed in the Discussion and Conclusion section.

Minor concerns:

1. In the Discussion section, several passages are repetitive and overly descriptive, reiterating results already presented in detail in the Results section rather than providing higher-level synthesis and interpretation. In particular, the discussion of frequency-dependent effects of repetitive magnetic stimulation (rMS) on cell proliferation and signaling pathways (approximately lines 399–410) essentially restates findings previously described in the Results. Similarly, the detailed recounting of the Jo et al. studies and Wnt/β-catenin pathway modulation (approximately lines 411–433) repeats the experimental details, including specific assays and molecular targets, rather than focusing on their broader biological implications. These repetitions diminish the Discussion's conceptual clarity and obscure opportunities for integrative interpretation across studies. Condensing these sections and shifting the emphasis toward comparative analysis, mechanistic synthesis, and identification of overarching patterns would significantly improve readability and strengthen the scientific contribution of the Discussion.

R: The discussion was rewriting focusing on possible action mechanisms. In addition, the discussion was subdivided into topics for a better understanding of the differences between the techniques.

2. It is worth considering adding a diagram summarizing the proposed mechanisms of sMS and rMS.

R: This will be uploaded after the final round of discussions.

3. Given the heterogeneity of responses to static and repetitive magnetic stimulation across tumor models, I wonder whether the authors could briefly comment on whether any potential molecular or cellular markers of response can be tentatively inferred from the reviewed studies. Even a short statement addressing possible candidate pathways, or explicitly noting that the current evidence is insufficient to identify such markers, would further strengthen the Discussion.

R: The discussion was subdivided into topics, thus facilitating the comparison between the two techniques and a better understanding of the different pathways and markers involved in their effects on each type of tumor.

4. I recognize that this manuscript is a scoping review and that a quantitative synthesis is not required. However, I would be interested if the Authors could briefly comment in the Discussion on whether any qualitative or approximate quantitative trends (for example, related to stimulation intensity, frequency, or exposure duration) can be inferred from the available studies, or note that the current evidence does not allow such conclusions.

R: These topics were best addressed in the discussion, emphasizing the differences between stimulation intensity, frequency, and exposure duration.

 

Comments on the Quality of English Language

While the English is generally clear, several sentences are overly long or awkwardly structured, particularly in the Introduction (e.g., lines ~45–52, ~73–81) and Discussion (e.g., lines ~399–406, ~411–418), and would benefit from stylistic simplification.

R: Considering the high cost of having an English proofreader done by a native speaker and the short time available for manuscript revision, we attempt to improve the quality of the English and, if the revision is accepted, we assume responsibility for having the English proofread.

Reviewer 2 Report

Comments and Suggestions for Authors

In this review entitled “Molecular and cellular mechanisms of static and repetitive magnetic stimulation in cancer therapy: a scoping review,” the authors present a comprehensive overview of preclinical studies (in vitro and in vivo rodent models) investigating repetitive magnetic stimulation (rMS/rTMS) and static magnetic stimulation (sMS/SMF) as potential adjuvant anti-tumoral strategies. The review summarizes stimulation devices, experimental parameters, and reported biological outcomes, and appropriately highlights the substantial heterogeneity in protocols as well as the mixed responses observed across different cancer cell types. The authors conclude that magnetic stimulation holds promise as an adjuvant therapeutic approach, but that further standardization, mechanistic clarification, and safety evaluation are required. Overall, the manuscript addresses a timely and focused topic with clear translational relevance. However, several concerns should be addressed, as outlined below:

1. I did not identify any formal appraisal of study quality or risk of bias in either the Methods or Results sections. While the Methods describe the extraction of study characteristics, no structured risk-of-bias evaluation is reported. Given the limited number of available studies and the marked methodological heterogeneity, inclusion of at least a basic quality assessment is essential to allow readers to better judge the strength and reliability of the preclinical evidence.

2. The manuscript specifies the databases searched and provides general keywords, but does not report the complete, reproducible search strings for each database or the exact dates on which the searches were performed. In addition, neither the detailed search strategy nor a PRISMA-ScR checklist is provided as supplementary material. Although PRISMA flow diagrams (Figures 1 and 2) are included, full search details are necessary to ensure transparency and reproducibility.

3. The review clearly documents substantial heterogeneity in stimulation frequency, field intensity, exposure duration, device/coil configuration, and assessed biological endpoints. However, this heterogeneity currently limits the utility of the review for guiding experimental design. The manuscript would benefit from a more structured synthesis, such as subgroup analyses or comparative summaries (e.g., low- versus high-frequency stimulation and associated biological responses across different cancer types).

4. While the authors list the devices used across studies, there is no systematic discussion of dosimetric considerations, including magnetic field mapping, spatial gradients, distance between the source and the biological sample, or potential thermal artifacts. These factors are critical for experimental reproducibility and are particularly important for translation from in vitro systems to animal models and, ultimately, to clinical applications.

5. Although the authors acknowledge the need for toxicological evaluation, the manuscript does not outline specific preclinical safety studies or regulatory considerations required to advance from rodent models toward clinical trials. The translational section should be expanded to include a pragmatic roadmap, detailing recommended toxicology endpoints, good laboratory practice (GLP) considerations, device certification requirements, and key elements for the design of first-in-human studies.

Author Response

Reviewer 2

Date of this review: 16 Jan 2026 16:51:38

Quality of English Language: The English is fine and does not require any improvement.

Comments and Suggestions for Authors

In this review entitled “Molecular and cellular mechanisms of static and repetitive magnetic stimulation in cancer therapy: a scoping review,” the authors present a comprehensive overview of preclinical studies (in vitro and in vivo rodent models) investigating repetitive magnetic stimulation (rMS/rTMS) and static magnetic stimulation (sMS/SMF) as potential adjuvant anti-tumoral strategies. The review summarizes stimulation devices, experimental parameters, and reported biological outcomes, and appropriately highlights the substantial heterogeneity in protocols as well as the mixed responses observed across different cancer cell types. The authors conclude that magnetic stimulation holds promise as an adjuvant therapeutic approach, but that further standardization, mechanistic clarification, and safety evaluation are required. Overall, the manuscript addresses a timely and focused topic with clear translational relevance. However, several concerns should be addressed, as outlined below:

1. I did not identify any formal appraisal of study quality or risk of bias in either the Methods or Results sections. While the Methods describe the extraction of study characteristics, no structured risk-of-bias evaluation is reported. Given the limited number of available studies and the marked methodological heterogeneity, inclusion of at least a basic quality assessment is essential to allow readers to better judge the strength and reliability of the preclinical evidence.

R: The risk of bias of the included studies was assessed independently for in vitro and in vivo studies using validated, study-design–specific instruments. In vitro studies were evaluated with the QUIN (Quality Assessment Tool for In Vitro Studies) tool [1]. In vivo studies were assessed using the SYRCLE Risk of Bias tool for animal studies [2]. Two reviewers independently conducted all risk-of-bias assessments, with discrepancies resolved through discussion when necessary. 

[1] Sheth, V. H.; Shah, N. P.; Jain, R.; Bhanushali, N.; Bhatnagar, V. Development and validation of a risk-of-bias tool for assessing in vitro studies conducted in dentistry: The QUIN. J Prosthet Dent.  2024, 128(6), 695–703. https://doi.org/10.1016/j.prosdent.2022.05.019

[2] Hooijmans, C.R.; Rovers, M.M.; de Vries, R.B.; Leenaars, M.; Ritskes-Hoitinga, M.; Langendam, M.W. SYRCLE's risk of bias tool for animal studies. BMC Med Res Methodol. 2014, 26, 14:43. doi: 10.1186/1471-2288-14-43

2. The manuscript specifies the databases searched and provides general keywords, but does not report the complete, reproducible search strings for each database or the exact dates on which the searches were performed. In addition, neither the detailed search strategy nor a PRISMA-ScR checklist is provided as supplementary material. Although PRISMA flow diagrams (Figures 1 and 2) are included, full search details are necessary to ensure transparency and reproducibility.

R: The search syntax used in each of the databases and the PRISMA ScR checklist and included supplementary material files.

3. The review clearly documents substantial heterogeneity in stimulation frequency, field intensity, exposure duration, device/coil configuration, and assessed biological endpoints. However, this heterogeneity currently limits the utility of the review for guiding experimental design. The manuscript would benefit from a more structured synthesis, such as subgroup analyses or comparative summaries (e.g., low- versus high-frequency stimulation and associated biological responses across different cancer types).

R: The discussion was subdivided into topics, thus facilitating the comparison between the techniques and tumor types. It provided a better understanding of the different pathways and markers involved in MS effects on each type of tumor.

4. While the authors list the devices used across studies, there is no systematic discussion of dosimetric considerations, including magnetic field mapping, spatial gradients, distance between the source and the biological sample, or potential thermal artifacts. These factors are critical for experimental reproducibility and are particularly important for translation from in vitro systems to animal models and, ultimately, to clinical applications.

R: This review revealed that most studies did not present a complete and detailed description of the stimulation protocols used. Likewise, the studies do not present the stimulation parameters and experimental design in an organized and detailed manner. Future research should prioritize the systematic optimization of stimulation parameters, seeking greater translationality of the study, and thus clarify the conditions under which magnetic stimulation can produce reproducible and clinically relevant effects.

5. Although the authors acknowledge the need for toxicological evaluation, the manuscript does not outline specific preclinical safety studies or regulatory considerations required to advance from rodent models toward clinical trials. The translational section should be expanded to include a pragmatic roadmap, detailing recommended toxicology endpoints, good laboratory practice (GLP) considerations, device certification requirements, and key elements for the design of first-in-human studies.

R: Thank you for your consideration. However, it is important to emphasize that the present scoping review did not aim to evaluate the regulatory or safety aspects of magnetic stimulation, but rather to identify research investigating the effects of sMS and rMS in both in vitro and in vivo trials to evaluate protocols and their impacts on morphological and molecular parameters. These points could be addressed in a future review.

Reviewer 3 Report

Comments and Suggestions for Authors

Overview of the Manuscript
This manuscript presents a comprehensive scoping review of the use of repetitive magnetic stimulation (rMS) and static magnetic stimulation (sMS) as potential adjunctive therapies in cancer, with a focus on in vitro and in vivo preclinical models. The review highlights that low-frequency rMS shows more consistent tumor-suppressive effects, while sMS demonstrates more variable and cell-type–dependent results. The authors conclude that magnetic stimulation holds promise as a complementary anticancer strategy but emphasize the need for standardized protocols and deeper mechanistic understanding.

 

GENERAL COMMENT
The work is of interest because it aligns with the growing focus on non-invasive modulatory and biophysical approaches in oncology, particularly in addressing the challenges of treating glioblastoma. The review is well structured and sufficiently informative; the effort devoted to literature collection, protocol classification, and mechanistic interpretation is appreciable. However, the manuscript has several weaknesses in terms of clarity, consistency, methodological transparency, and language quality that should be addressed. Furthermore, several issues (see comments below) should be more thoroughly discussed and developed in order to enhance the manuscript’s novelty and scientific contribution.

 

 SPECIFIC COMMENTS

Introduction
Pag. 2, line 89: Correct the conceptual statement: “reduce,” not “induce cisplatin resistance”.

Pag. 2–3, lines 92–102: This paragraph is redundant and does not add significant information. It should be substantially reduced or deleted.

 

Materials and Methods
Pag. 3, lines 126–130: The use of the keywords “pulsed magnetic field,” “rMS,” “rTMS,” and “magnetic field” is inconsistent and may affect readability. “Pulsed magnetic field” is often associated with a distinct body of literature (please clarify whether it is included or excluded), and it is conceptually different from rTMS/rMS. The distinctions among rMS, rTMS, and sMS should be more clearly operationalized.

Pag. 3–4, lines 131–149: The inclusion criteria allow studies using chemotherapy “assuming that MS was also employed,” while the exclusion criteria remove studies in which MS is not used as an adjunctive therapy. This creates a potential logical inconsistency. Please clarify this statement.

Additionally, results should be clearly stratified based on “MS alone” versus “MS combined with other therapies.”

 

Discussion
The Discussion section contains repeated descriptions of protocols, mechanisms, and outcomes. Please revise and condense this section.

Multiple mechanisms are discussed (ROS, Ca²⁺ signaling, autophagy, Wnt/β-catenin, ERK/AKT, EMT), but they are not sufficiently integrated into a unified mechanistic framework. The authors are encouraged to provide a more coherent and integrative perspective on how these pathways may interact.

 Pag. 28, lines 526–533: The authors correctly highlight protocol heterogeneity, as also noted on Pag. 27, lines 448–450 and Pag. 28, lines 506–508; however, no formal risk-of-bias or study quality assessment is performed, even at a descriptive level. The inclusion of a basic methodological quality appraisal (e.g., an adapted SYRCLE risk-of-bias tool for animal studies or a simple internal validity checklist) is strongly recommended.

An adequate section on “potential for clinical application” should be developed. Differences in magnetic field penetration, dosimetry, and scaling between rodents, cell cultures, and humans are not critically addressed. Safety claims are based on limited organ histology and short-term exposure. A subsection on translational limitations—such as tumor depth and human safety thresholds—should be included.

 Discussion/Conclusion
Pag. 28, lines 519–522 and 536–538: The safety discussion is limited and largely speculative. Please expand this section to address potential genotoxicity and long-term exposure risks in greater detail.

Comments on the Quality of English Language

The manuscript contains several grammatical and typographical errors; professional language editing is strongly recommended.

Author Response

Reviewer 3

Date of this review: 18 Jan 2026 17:09:50

Quality of English Language: The English could be improved to more clearly express the research.

R: Considering the high cost of having an English proofreader done by a native speaker and the short time available for manuscript revision, we attempt to improve the quality of the English and, if the revision is accepted, we assume responsibility for having the English proofread.

Comments and Suggestions for Authors

Overview of the Manuscript

This manuscript presents a comprehensive scoping review of the use of repetitive magnetic stimulation (rMS) and static magnetic stimulation (sMS) as potential adjunctive therapies in cancer, with a focus on in vitro and in vivo preclinical models. The review highlights that low-frequency rMS shows more consistent tumor-suppressive effects, while sMS demonstrates more variable and cell-type–dependent results. The authors conclude that magnetic stimulation holds promise as a complementary anticancer strategy but emphasize the need for standardized protocols and deeper mechanistic understanding.

GENERAL COMMENT

The work is of interest because it aligns with the growing focus on non-invasive modulatory and biophysical approaches in oncology, particularly in addressing the challenges of treating glioblastoma. The review is well structured and sufficiently informative; the effort devoted to literature collection, protocol classification, and mechanistic interpretation is appreciable. However, the manuscript has several weaknesses in terms of clarity, consistency, methodological transparency, and language quality that should be addressed. Furthermore, several issues (see comments below) should be more thoroughly discussed and developed in order to enhance the manuscript’s novelty and scientific contribution.

SPECIFIC COMMENTS

1. Introduction

Pag. 2, line 89: Correct the conceptual statement: “reduce,” not “induce cisplatin resistance”. 

R: Thank you for your attention. This has been corrected.

Pag. 2–3, lines 92–102: This paragraph is redundant and does not add significant information. It should be substantially reduced or deleted. 

R: Thank you for noticing this. The paragraph has been rewritten for better understanding.

2. Materials and Methods
3. a) Pag. 3, lines 126–130: The use of the keywords “pulsed magnetic field,” “rMS,” “rTMS,” and “magnetic field” is inconsistent and may affect readability. “Pulsed magnetic field” is often associated with a distinct body of literature (please clarify whether it is included or excluded), and it is conceptually different from rTMS/rMS. The distinctions among rMS, rTMS, and sMS should be more clearly operationalized.

R: Thank you for your comment. The acronyms sMS, sMF, PEMF (or pulsed MF), rMS, and rTMS are sometimes used interchangeably; however, they refer to conceptually and technically distinct neuromodulation approaches. To avoid conceptual overlap and to guarantee appropriate interpretation and comparison of neuromodulation studies, it is imperative to make these distinctions clear. 

In this version, we have added the item "Terminology" to the Materials and Methods section for better clarification of these techniques.

1. b) Pag. 3–4, lines 131–149: The inclusion criteria allow studies using chemotherapy “assuming that MS was also employed,” while the exclusion criteria remove studies in which MS is not used as an adjunctive therapy. This creates a potential logical inconsistency. Please clarify this statement.

R: Thank you for your contribution. We improved the wording of the sentence for better understanding and to avoid confusion in the interpretation of this information. We made it clear that only studies involving MS techniques would be included in the review.

Item Results of Abstract (page 1): Studies utilizing rMS or sMS as a treatment for conditions other than cancers, as well as those not considering these therapies as adjunctive therapy, were eliminated.

1. c) Additionally, results should be clearly stratified based on “MS alone” versus “MS combined with other therapies.”

R: There is already a topic sMS combined with antitumor drugs in Results and Discussion sessions

3. Discussion
4. a) The Discussion section contains repeated descriptions of protocols, mechanisms, and outcomes. Please revise and condense this section.

R: The discussion was rewriting focusing on possible action mechanisms. In addition, the discussion was subdivided into topics for a better understanding of the differences between the techniques.

1. b) Multiple mechanisms are discussed (ROS, Ca²⁺ signaling, autophagy, Wnt/β-catenin, ERK/AKT, EMT), but they are not sufficiently integrated into a unified mechanistic framework. The authors are encouraged to provide a more coherent and integrative perspective on how these pathways may interact.

R: The discussion was rewriting focusing on possible action mechanisms in a more integrated way. 

1. c) Pag. 28, lines 526–533: The authors correctly highlight protocol heterogeneity, as also noted on Pag. 27, lines 448–450 and Pag. 28, lines 506–508; however, no formal risk-of-bias or study quality assessment is performed, even at a descriptive level. The inclusion of a basic methodological quality appraisal (e.g., an adapted SYRCLE risk-of-bias tool for animal studies or a simple internal validity checklist) is strongly recommended.

R: The risk of bias of the included studies was assessed independently for in vitro and in vivo studies using validated, study-design–specific instruments. In vitro studies were evaluated with the QUIN (Quality Assessment Tool for In Vitro Studies) tool [1]. In vivo studies were assessed using the SYRCLE Risk of Bias tool for animal studies [2]. Two reviewers independently conducted all risk-of-bias assessments, with discrepancies resolved through discussion when necessary. 

[1] Sheth, V. H.; Shah, N. P.; Jain, R.; Bhanushali, N.; Bhatnagar, V. Development and validation of a risk-of-bias tool for assessing in vitro studies conducted in dentistry: The QUIN. J Prosthet Dent.  2024, 128(6), 695–703. https://doi.org/10.1016/j.prosdent.2022.05.019

[2] Hooijmans, C.R.; Rovers, M.M.; de Vries, R.B.; Leenaars, M.; Ritskes-Hoitinga, M.; Langendam, M.W. SYRCLE's risk of bias tool for animal studies. BMC Med Res Methodol. 2014, 26, 14:43. doi: 10.1186/1471-2288-14-43

1. d) An adequate section on “potential for clinical application” should be developed. Differences in magnetic field penetration, dosimetry, and scaling between rodents, cell cultures, and humans are not critically addressed. Safety claims are based on limited organ histology and short-term exposure. A subsection on translational limitations—such as tumor depth and human safety thresholds—should be included.

R: This review revealed that most studies did not present a complete and detailed description of the stimulation protocols used. Likewise, the studies do not present the stimulation parameters and experimental design in an organized and detailed manner. Future research should prioritize the systematic optimization of stimulation parameters, seeking greater translationality of the study, and thus clarify the conditions under which magnetic stimulation can produce reproducible and clinically relevant effects.

4. Discussion/Conclusion
5. a) Pag. 28, lines 519–522 and 536–538: The safety discussion is limited and largely speculative. Please expand this section to address potential genotoxicity and long-term exposure risks in greater detail.

R: The Discussion was rewritten and a paragraph was inserted in Page 39/first paragraph: Neuromodulatory techniques have been examined for their efficacy in treating brain tumors, focusing on the ability to modulate certain neuronal activities within the central nervous system. Although numerous studies indicate a favorable safety profile for exposure to magnetic fields, the need for systematic long-term toxicological investigations in organs, including bone marrow and the reproductive system, remains emphasized.

In addition, studies on the safety and potential genotoxicity of prolonged exposure to magnetic fields were not included in the literature search. Furthermore, this was not a primary objective of this scoping review. A future review of studies should be conducted to address these important aspects for the translationality of the findings.

Comments on the Quality of English Language

The manuscript contains several grammatical and typographical errors; professional language editing is strongly recommended.

R: Considering the high cost of having an English proofreader done by a native speaker and the short time available for manuscript revision, we attempt to improve the quality of the English and, if the revision is accepted, we assume responsibility for having the English proofread.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I want to thank the authors for their careful and thorough revision of the manuscript. The revised version shows clear improvements in structure and clarity, particularly in the Discussion section, which has been substantially reorganized to address better potential mechanisms underlying the effects of static and repetitive magnetic stimulation. A clearer distinction among biological pathways and responses greatly enhances the readability and scientific coherence of the review.
Importantly, the authors now more explicitly acknowledge the heterogeneity of experimental outcomes, especially in static magnetic stimulation, and highlight the context-dependent and sometimes conflicting biological effects observed across tumor models. This balanced interpretation enhances the manuscript's scientific rigor and reduces the risk of overgeneralization. The expanded discussion of methodological variability and translational considerations is also appreciated.
Overall, the authors have addressed the main concerns raised in the previous review, and the manuscript now provides a clear, comprehensive, and well-balanced overview of the current preclinical evidence. The revised version is suitable for publication after minor editorial refinement.

Comments on the Quality of English Language

While the manuscript would still benefit from minor stylistic polishing of the English language to further improve fluency, these issues do not detract from the overall scientific content. The addition of a schematic summary of the proposed mechanisms, as the authors mentioned, would further enhance the clarity of the review.

Reviewer 2 Report

Comments and Suggestions for Authors

The revised version of the manuscript shows a clear and substantial improvement compared with the previous submission. The authors have carefully addressed the main concerns raised during the peer-review process. These additions enhance the overall rigor and clarity of the manuscript. The authors have also provided reasonable and well-justified responses to the remaining comments. I have no further major concerns.

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript has been substantially improved in terms of overall structure, clarity, and presentation. The revisions have effectively strengthened the quality of the work, and the authors have carefully and thoroughly addressed all the concerns and comments previously raised.

No further major or minor concerns remain.