The review provides a useful synthesis of epigenetic mechanisms in brain metastasis, but several aspects of the published record appear to require clarification. First, Figure 2 reports cBioPortal-derived alteration frequencies, enrichment classifications, and Benjamini–Hochberg-adjusted significance without specifying the primary-tumor comparator groups, alteration classes, gene-specific denominators, complete tested-gene set, or underlying contingency tables. Some reported percentages also cannot be calculated from the displayed overall cohort sizes, potentially because of gene-dependent MSK-IMPACT coverage; could the authors provide the original cBioPortal export, case definitions, effective denominators, and statistical output needed to reproduce the figure?
Second, the therapeutic section presents NCT02429570 in the context of FTO inhibition, although the brain-metastasis rationale for this meclofenamate trial appears to concern inhibition of Cx43-mediated gap-junction signaling rather than clinical evaluation of FTO inhibition. Figure 3 similarly appears to combine FTO regulation with the tumor-derived EV/miR-181c/PDPK1 pathway without citing evidence for that direct mechanistic connection. Could the authors clarify whether these links are experimentally demonstrated or represent a synthesis of independent findings?