Knockdown of Claudin-8 (CLDN8) Indicates a Link Between Breast Cancer Cell Sensitivity to Chemotherapeutics and Reveals a Potential Use of CLDN8 as a Molecular Diagnostic and Target for Therapy.

Similarly, MDA-MB-231 cells (ER − , serving as a control for off-target effects) showed that WT cells were moderately inhibited by a high dose of Tamoxifen, while CLDN8KD cells were even less affected, culminating in a highly significant difference in cell growth by day 5 (***, p < 0.001).

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Notably, statistically significant differences in IC50 values were observed for endocrine therapies (e.g., Tamoxifen, p < 0.01) and HER2-targeted agents (e.g., Lapatinib, p < 0.05), whereas differences for chemotherapeutics such as Cisplatin and Methotrexate did not reach statistical significance ( p > 0.05).

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Notably, when considering intrinsic subtypes, as shown in Figure 6 , luminal A patients (typically low-grade ER + tumors) had the most pronounced CLDN8-related benefit, whereas the luminal B subgroup (often more proliferative or HER2 + ER + tumors; Figure 6 F) showed a positive trend that did not reach strong significance.

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