Exploitation of sulfated glycosaminoglycan status for precision medicine of platinums in triple-negative breast cancer

摘要: Triple negative breast cancer (TNBC) is a subtype of lacking targetable biomarkers. TNBC known to be most aggressive, and when metastatic often drug resistant uncurable. Biomarkers predicting response therapy improve treatment decisions allow personalized approaches for patients. This study explores sulfated glycosaminoglycan (sGAG) levels as predictor platinum therapy. sGAG were quantified in three distinct tumor models including cell line-derived, patient-derived xenograft (PDX) tumors, isogenic deficient biosynthesis. The vivo antitumor efficacy Triplatin, sGAG-directed agent, was compared these the clinical carboplatin. We determined that >40% PDX tissue microarray samples have high sGAGs. accumulation Triplatin tumors well positively correlated with on cells, whereas carboplatin followed opposite trend. In carboplatin-resistant expressing sGAGs, decreased primary growth, reduced lung metastases inhibited growth lungs, liver, ovaries. served sensitivity TNBC. may particularly beneficial treating patients chemotherapy-resistant who evidence residual disease after standard neoadjuvant chemotherapy. More effective adjuvant will likely outcome SignificanceTNBC heterogenous disease, defined by absence therapeutic target. Our recent results show sGAGs provide viable biomarker TNBC, producing significant advantage over this setting. Selective precision medicine agents, such are active against exploit molecular biomarkers like significantly benefit