Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies
Abstract
1. Introduction
2. Triple Negative Breast Cancer (TNBC)
3. Current TNBC Treatment Paradigms
4. Prognosis and Treatment Heterogeneity in TNBC
5. Newly FDA-Approved Targeted Therapies for TNBC
5.1. Immune Checkpoint Blockade Therapies
5.2. PARP Inhibitors
5.3. Anti-Trop2 Antibody Drug Conjugate Therapy in TNBC
6. Emerging Targeted Therapies in TNBC
6.1. EGFR Targeted Therapy in TNBC
6.2. VEGF Targeted Therapy in TNBC
6.3. PI3K/AKT/mTOR Targeted Therapy in TNBC
6.4. AR Targeted Therapy in TNBC
6.5. ERβ Targeted Therapy in TNBC
7. K-RAS/SIAH is a Major Tumor-Driving Signaling Pathway in TNBC
7.1. SIAH’s Gatekeeper Role is Indispensable for Proper K-RAS/EGFR Signal Transduction
7.2. K-RAS/SIAH/EGFR Pathway is Commonly Activated in TNBC, and SIAH is a Therapy-Responsive and Prognostic Biomarker in TNBC
7.3. SIAH as an Actionable Target Against EGFR-Driven TNBC.
8. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ACT | Adriamycin: Cytoxan, and Taxotere |
AR | Androgen receptor |
CI | confidence interval |
DFS | disease-free survival |
DRFS | distant recurrence-free survival |
EGFR | epidermal growth factor receptor |
ER | estrogen receptor |
HER2 | human epidermal growth factor receptor 2 |
H&E | hematoxylin and eosin staining |
HR | Hazard Ratio |
IDFS | invasive disease-free survival |
IHC | immunohistochemistry |
LN | lymph node |
MBC | metastatic breast cancer |
mTNBC | metastatic TNBC |
mTOR | the mammalian target of rapamycin |
NACT | neoadjuvant chemotherapy |
OS | overall survival |
PARP | poly-ADP-ribose polymerase |
pCR | pathological complete response |
PD-1 | programmed cell death receptor-1 |
PD-L1 | programmed death ligand-1 |
PFS | progression-free survival |
PI3K | phosphoinositide-3 kinase |
pIR | pathological incomplete response |
PKB | protein kinase B (AKT) |
PR | progesterone receptor |
RCB | Residual Cancer Burden |
SEER | Surveillance, Epidemiology and End Results Program |
SIAH | human homologues of Drosophila Seven-In-Absentia |
SOC | standard of care |
TIL | tumor infiltrating lymphocytes |
TME | tumor microenvironment |
TNBC | triple-negative breast cancer |
TNM | tumor size, lymph node status, metastasis |
Trop-2 | Trophoblast cell-surface antigen |
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Gupta, G.K.; Collier, A.L.; Lee, D.; Hoefer, R.A.; Zheleva, V.; Siewertsz van Reesema, L.L.; Tang-Tan, A.M.; Guye, M.L.; Chang, D.Z.; Winston, J.S.; et al. Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies. Cancers 2020, 12, 2392. https://doi.org/10.3390/cancers12092392
Gupta GK, Collier AL, Lee D, Hoefer RA, Zheleva V, Siewertsz van Reesema LL, Tang-Tan AM, Guye ML, Chang DZ, Winston JS, et al. Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies. Cancers. 2020; 12(9):2392. https://doi.org/10.3390/cancers12092392
Chicago/Turabian StyleGupta, Gagan K., Amber L. Collier, Dasom Lee, Richard A. Hoefer, Vasilena Zheleva, Lauren L. Siewertsz van Reesema, Angela M. Tang-Tan, Mary L. Guye, David Z. Chang, Janet S. Winston, and et al. 2020. "Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies" Cancers 12, no. 9: 2392. https://doi.org/10.3390/cancers12092392
APA StyleGupta, G. K., Collier, A. L., Lee, D., Hoefer, R. A., Zheleva, V., Siewertsz van Reesema, L. L., Tang-Tan, A. M., Guye, M. L., Chang, D. Z., Winston, J. S., Samli, B., Jansen, R. J., Petricoin, E. F., Goetz, M. P., Bear, H. D., & Tang, A. H. (2020). Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies. Cancers, 12(9), 2392. https://doi.org/10.3390/cancers12092392