136P Molecular correlates of drug response to guide therapy in TNBC

• DOI: 10.1016/j.esmoop.2023.101946
• Publication Date: 2023-10-06T10:10:20Z
• Authors: N. Merrill; N. Vandecan; A. Apfel; H. Serhan; P. Ulintz; L. Bao; A. Morikawa; M. Soellner; S. Merajver
• Keywords: Drug response; Triple-negative breast cancer; Targeted Therapy; Personalized Medicine

TNBC is more likely to metastasize within 3-5 years than other forms of breast cancer and has a median survival 17.6-21.3 months after metastasis. Recent advances are promising, but trial results immunotherapy-chemo combinations have resulted in 3-year overall rate under 36% PD-L1 based cohort. There thus an unmet need for innovations that lead new treatments improve outcomes patients with personalized manner. We developed platform identify predictors drug efficacy TNBC. assembled panel models were screened library 387 compounds. integrated these multiomic molecular characterization significant correlates response therapy. used RNA characterize treatment naive PDXs predict one the most promising drugs, SN-38, known active evaluated SN-38 vivo ensure our vitro screening was indicative response. Following screening, we prioritized 35 drugs on their activity variance response, identifying statistically 27 out (77%) Focusing identified Utilizing rapid profiling, predicted previously untested SN-38. Ex evaluation 5 revealed predictions correlated actual autophagy AKT pathways elevated poor SN-38; specific co-targeting effective strategy rational, synergistic combinations. In irinotecan (SN-38 pro-drug) demonstrated correlation between assayed mice. compounds These demonstrate promise prediction molecularly unknown samples as well identification companion therapeutics synergize given therapy help prevent or delay resistance. Going forward, working validation