Title: Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects
on patients' FOXP1 and GGT levels
Version: 0 Date: 25 Nov 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors , please address the following points below:
-While the clinical outcomes and biomarker changes are reported, the study would benefit
from a deeper exploration of the mechanisms by which capecitabine specifically enhances
oxaliplatin sensitivity at the molecular level. Additional data on the molecular interactions or
signaling pathways—such as DNA repair mechanisms and apoptosis pathways—would improve
the understanding of the synergy between the two drugs.
-The statistical methods employed are generally sound; however, providing more information
on the corrections for multiple comparisons and potential confounders (such as patient age and
prior treatments) would be beneficial.
-Although the correlation between drug sensitivity and FOXP1/GGT levels is intriguing, there
is limited explanation regarding the underlying biology. How do changes in FOXP1 expression
affect drug metabolism or resistance pathways in gastric cancer cells? Additionally, does GGT
influence capecitabine metabolism or the cellular response to oxidative stress induced by
oxaliplatin?
-While FOXP1 and GGT levels were assessed, further validation in independent cohorts and
through different platforms, such as proteomics and gene expression profiling, would strengthen
their role as reliable biomarkers for predicting treatment outcomes.
-It would also be helpful to evaluate whether the relationship between FOXP1/GGT and
treatment response is consistent across various patient subgroups (e.g., age, gender, tumor
stage, prior therapies). This could help identify subpopulations more likely to benefit from the
combination therapy.
-The study does not examine other potential factors that could influence drug sensitivity, such
as genetic or epigenetic changes, tumor microenvironment factors, or variations in immune
response. Acknowledging these variables would strengthen the discussion and suggest ways
they could be integrated into future studies.
-The role of FOXP1 in cancer is complex; it can function as both a tumor suppressor and an
oncogene, depending on the context. Further clarification of FOXP1’s specific role in gastric
cancer and how it modulates drug response in this particular setting would enrich the discussion.
Title: Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects
on patients' FOXP1 and GGT levels
Version: 0 Date: 25 Nov 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors , please address the following points below:
-While the clinical outcomes and biomarker changes are reported, the study would benefit
from a deeper exploration of the mechanisms by which capecitabine specifically enhances
oxaliplatin sensitivity at the molecular level. Additional data on the molecular interactions or
signaling pathways—such as DNA repair mechanisms and apoptosis pathways—would improve
the understanding of the synergy between the two drugs.
-The statistical methods employed are generally sound; however, providing more information
on the corrections for multiple comparisons and potential confounders (such as patient age and
prior treatments) would be beneficial.
-Although the correlation between drug sensitivity and FOXP1/GGT levels is intriguing, there
is limited explanation regarding the underlying biology. How do changes in FOXP1 expression
affect drug metabolism or resistance pathways in gastric cancer cells? Additionally, does GGT
influence capecitabine metabolism or the cellular response to oxidative stress induced by
oxaliplatin?
-While FOXP1 and GGT levels were assessed, further validation in independent cohorts and
through different platforms, such as proteomics and gene expression profiling, would strengthen
their role as reliable biomarkers for predicting treatment outcomes.
-It would also be helpful to evaluate whether the relationship between FOXP1/GGT and
treatment response is consistent across various patient subgroups (e.g., age, gender, tumor
stage, prior therapies). This could help identify subpopulations more likely to benefit from the
combination therapy.
-The study does not examine other potential factors that could influence drug sensitivity, such
as genetic or epigenetic changes, tumor microenvironment factors, or variations in immune
response. Acknowledging these variables would strengthen the discussion and suggest ways
they could be integrated into future studies.
-The role of FOXP1 in cancer is complex; it can function as both a tumor suppressor and an
oncogene, depending on the context. Further clarification of FOXP1’s specific role in gastric
cancer and how it modulates drug response in this particular setting would enrich the discussion.
Please review this paper.
user
Title: Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects
on patients' FOXP1 and GGT levels
Version: 0 Date: 25 Nov 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors , please address the following points below:
-While the clinical outcomes and biomarker changes are reported, the study would benefit
from a deeper exploration of the mechanisms by which capecitabine specifically enhances
oxaliplatin sensitivity at the molecular level. Additional data on the molecular interactions or
signaling pathways—such as DNA repair mechanisms and apoptosis pathways—would improve
the understanding of the synergy between the two drugs.
-The statistical methods employed are generally sound; however, providing more information
on the corrections for multiple comparisons and potential confounders (such as patient age and
prior treatments) would be beneficial.
-Although the correlation between drug sensitivity and FOXP1/GGT levels is intriguing, there
is limited explanation regarding the underlying biology. How do changes in FOXP1 expression
affect drug metabolism or resistance pathways in gastric cancer cells? Additionally, does GGT
influence capecitabine metabolism or the cellular response to oxidative stress induced by
oxaliplatin?
-While FOXP1 and GGT levels were assessed, further validation in independent cohorts and
through different platforms, such as proteomics and gene expression profiling, would strengthen
their role as reliable biomarkers for predicting treatment outcomes.
-It would also be helpful to evaluate whether the relationship between FOXP1/GGT and
treatment response is consistent across various patient subgroups (e.g., age, gender, tumor
stage, prior therapies). This could help identify subpopulations more likely to benefit from the
combination therapy.
-The study does not examine other potential factors that could influence drug sensitivity, such
as genetic or epigenetic changes, tumor microenvironment factors, or variations in immune
response. Acknowledging these variables would strengthen the discussion and suggest ways
they could be integrated into future studies.
-The role of FOXP1 in cancer is complex; it can function as both a tumor suppressor and an
oncogene, depending on the context. Further clarification of FOXP1’s specific role in gastric
cancer and how it modulates drug response in this particular setting would enrich the discussion.
assistant