biostudies-literatureVasudevan SIsrael Science FoundationNational Institutes of HealthNIH HHS5009https://www.ebi.ac.uk/biostudies/studies/S-EPMC8507629biostudies-literatureUnknown13(19)Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancers which is treated mainly with chemotherapy and radiotherapy. Epidermal growth factor receptor (EGFR) was considered to be frequently expressed in TNBC, and therefore was suggested as a therapeutic target. However, clinical trials of EGFR inhibitors have failed. In this study, we examine the relationship between the patient-specific TNBC network structures and possible mechanisms of resistance to anti-EGFR therapy. Using an information-theoretical analysis of 747 breast tumors from the TCGA dataset, we resolved individualized protein network structures, namely patient-specific signaling signatures (PaSSS) for each tumor. Each PaSSS was characterized by a set of 1-4 altered protein-protein subnetworks. Thirty-oneCancersDrug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures.PMC85076291961/19U01 CA238720Roy Chowdhury SAdejumobi IAAlkhatib HStefansky SVasudevan SKravchenko-Balasha NRubinstein AMfalseDrug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures.Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancers which is treated mainly with chemotherapy and radiotherapy. Epidermal growth factor receptor (EGFR) was considered to be frequently expressed in TNBC, and therefore was suggested as a therapeutic target. However, clinical trials of EGFR inhibitors have failed. In this study, we examine the relationship between the patient-specific TNBC network structures and possible mechanisms of resistance to anti-EGFR therapy. Using an information-theoretical analysis of 747 breast tumors from the TCGA dataset, we resolved individualized protein network structures, namely patient-specific signaling signatures (PaSSS) for each tumor. Each PaSSS was characterized by a set of 1-4 altered protein-protein subnetworks. Thirty-one2021-01-01T00:00:00Z2021 Oct2025-08-27T03:07:20.851Z2025-06-01T04:24:17.3ZS-EPMC85076293463849210.3390/cancers13195009