Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Culture
2.2. Survival Assay
2.3. Cell Fixation and Permeabilization of Phosphoproteins for Flow Cytometry
2.4. Flow Cytometry Analysis
2.5. Animal Studies
2.6. Western Blot Analysis
2.7. PaSSS Analysis
2.8. Selection of TNBC Cell Lines for Experimental Validation of the PaSSS-Based Strategy
2.9. Computational Single Data Analysis for Calculation of Cell-Specific Signaling Signatures (CSSS)
3. Results
3.1. Resolution of the Signaling Structures in Breast Cancer Patients Suggests That Anti-EGFR Monotherapy Should Be Inefficient in TNBC in Contrast to Anti-ER Therapies
3.2. The PaSSS-Based Strategy Suggests How Anti-EGFR/Anti-ER Therapies Should Be Incorporated in Order to Reduce Efficiently the Individualized Signaling Fluxes and Cell Regrowth
3.3. Rationally Designed PaSSS-Based Drug Combinations Prevented the Development of Drug Resistance
3.4. Monotherapies and Wrong Drug Combinations Do Not Deplete the Signaling of the TNBC Cell Lines but Induce a Switch from One Signaling State to Another
3.5. The Predicted Drug Combinations Are Selective and Efficient in Preventing the Development of Tumor Regrowth In Vivo
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Vasudevan, S.; Adejumobi, I.A.; Alkhatib, H.; Roy Chowdhury, S.; Stefansky, S.; Rubinstein, A.M.; Kravchenko-Balasha, N. Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures. Cancers 2021, 13, 5009. https://doi.org/10.3390/cancers13195009
Vasudevan S, Adejumobi IA, Alkhatib H, Roy Chowdhury S, Stefansky S, Rubinstein AM, Kravchenko-Balasha N. Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures. Cancers. 2021; 13(19):5009. https://doi.org/10.3390/cancers13195009
Chicago/Turabian StyleVasudevan, Swetha, Ibukun A. Adejumobi, Heba Alkhatib, Sangita Roy Chowdhury, Shira Stefansky, Ariel M. Rubinstein, and Nataly Kravchenko-Balasha. 2021. "Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures" Cancers 13, no. 19: 5009. https://doi.org/10.3390/cancers13195009