C188-9 reduces patient-specific primary breast cancer cells proliferation at the low, clinic-relevant concentration

Objectives: STAT3 is a key transcriptional activator of oncogenes in breast cancer, making it a potential therapeutic target. This study explores the therapeutic potential of C188-9, a STAT3 signaling pathway inhibitor, for breast cancer treatment using a novel pre-clinical platform with patient-specific primary cells (PSPCs).

Methods: PSPCs were isolated from breast cancer biopsy or surgical samples from fifteen patients with full consent. These cells were treated with C188-9 or other chemotherapy agents and assessed for viability through cell viability assays. The expression and activity of the STAT3 signaling pathway were evaluated using Western blot and real-time quantitative PCR.

Results: Treatment with C188-9 at the standard experimental concentration effectively inhibited PSPC proliferation. Moreover, when applied at a lower, clinically relevant concentration over an extended period, C188-9 further reduced PSPC viability, outperforming some traditional chemotherapy drugs. C188-9 also reduced pSTAT3 expression in PSPCs from certain patient samples, though not all. The drug inhibited breast cancer cell viability by targeting the STAT3-C-myc signaling pathway.

Conclusions: This study demonstrates that C188-9, tested at a low, clinically relevant dose alongside traditional chemotherapy agents, showed effectiveness in ten out of fifteen patient-derived PSPCs. In contrast, some conventional chemotherapy treatments failed. These findings suggest that C188-9 may offer targeted treatment for a subset of breast cancer patients, highlighting the potential for personalized treatment strategies using PSPCs.