PMID- 32846967
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231104
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 9
DP  - 2020 Aug 24
TI  - Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, 
      Unmet Needs, and Potential Targets for Future Therapies.
LID - 10.3390/cancers12092392 [doi]
LID - 2392
AB  - Triple-negative breast cancer (TNBC), characterized by the absence or low 
      expression of estrogen receptor (ER), progesterone receptor (PR), and human 
      epidermal growth factor receptor (HER2), is the most aggressive subtype of breast 
      cancer. TNBC accounts for about 15% of breast cancer cases in the U.S., and is 
      known for high relapse rates and poor overall survival (OS). Chemo-resistant TNBC 
      is a genetically diverse, highly heterogeneous, and rapidly evolving disease that 
      challenges our ability to individualize treatment for incomplete responders and 
      relapsed patients. Currently, the frontline standard chemotherapy, composed of 
      anthracyclines, alkylating agents, and taxanes, is commonly used to treat 
      high-risk and locally advanced TNBC. Several FDA-approved drugs that target 
      programmed cell death protein-1 (Keytruda) and programmed death ligand-1 
      (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates 
      (Trodelvy) have shown promise in improving clinical outcomes for a subset of 
      TNBC. These inhibitors that target key genetic mutations and specific molecular 
      signaling pathways that drive malignant tumor growth have been used as single 
      agents and/or in combination with standard chemotherapy regimens. Here, we review 
      the current TNBC treatment options, unmet clinical needs, and actionable drug 
      targets, including epidermal growth factor (EGFR), vascular endothelial growth 
      factor (VEGF), androgen receptor (AR), estrogen receptor beta (ERbeta), 
      phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR), and 
      protein kinase B (PKB or AKT) activation in TNBC. Supported by strong evidence in 
      developmental, evolutionary, and cancer biology, we propose that the K-RAS/SIAH 
      pathway activation is a major tumor driver, and SIAH is a new drug target, a 
      therapy-responsive prognostic biomarker, and a major tumor vulnerability in TNBC. 
      Since persistent K-RAS/SIAH/EGFR pathway activation endows TNBC tumor cells with 
      chemo-resistance, aggressive dissemination, and early relapse, we hope to design 
      an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy as a novel therapeutic 
      strategy to control and eradicate incurable TNBC in the future.
FAU - Gupta, Gagan K
AU  - Gupta GK
AD  - Leroy T. Canoles Jr. Cancer Research Center, Department of Microbiology and 
      Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23501, USA.
FAU - Collier, Amber L
AU  - Collier AL
AUID- ORCID: 0000-0002-5238-227X
AD  - DeWitt Daughtry Family Department of Surgery, Surgical Oncology, University of 
      Miami/Jackson Memorial Hospital, University of Miami Miller School of Medicine, 
      Miami, FL 33131, USA.
FAU - Lee, Dasom
AU  - Lee D
AD  - Department of Medicine, Internal Medicine, H. Lee Moffitt Cancer Center and 
      Research Institute, University of South Florida, Tampa, FL 33620, USA.
FAU - Hoefer, Richard A
AU  - Hoefer RA
AD  - Dorothy G. Hoefer Foundation, Sentara CarePlex Hospital, Newport News, VA 23666, 
      USA.
AD  - Sentara Cancer Network, Sentara Healthcare, Norfolk, VA 23507, USA.
FAU - Zheleva, Vasilena
AU  - Zheleva V
AD  - Surgical Oncology, Cancer Treatment Centers of America-Comprehensive Care and 
      Research Center Phoenix, 14200 W Celebrate Life Way, Goodyear, AZ 85338, USA.
FAU - Siewertsz van Reesema, Lauren L
AU  - Siewertsz van Reesema LL
AD  - Department of OB/GYN, University of Kentucky College of Medicine, University of 
      Kentucky, Lexington, KY 40536, USA.
FAU - Tang-Tan, Angela M
AU  - Tang-Tan AM
AD  - Department of Molecular and Cell Biology, UC Berkeley, Berkeley, CA 94720, USA.
FAU - Guye, Mary L
AU  - Guye ML
AUID- ORCID: 0000-0003-1622-8686
AD  - Sentara Cancer Network, Sentara Healthcare, Norfolk, VA 23507, USA.
AD  - Sentara Surgery Specialists, Sentara CarePlex Hospital, Newport News, VA 23666, 
      USA.
FAU - Chang, David Z
AU  - Chang DZ
AD  - Virginia Oncology Associates, 1051 Loftis Boulevard, Suite 100, Newport News, VA 
      23606, USA.
FAU - Winston, Janet S
AU  - Winston JS
AD  - Breast Pathology Services, Pathology Sciences Medical Group, Department of 
      Pathology, Sentara Norfolk General Hospital (SNGH), Norfolk, VA 23507, USA.
FAU - Samli, Billur
AU  - Samli B
AD  - Breast Pathology Services, Pathology Sciences Medical Group, Department of 
      Pathology, Sentara Norfolk General Hospital (SNGH), Norfolk, VA 23507, USA.
FAU - Jansen, Rick J
AU  - Jansen RJ
AUID- ORCID: 0000-0001-5683-2584
AD  - Department of Public Health, North Dakota State University, Fargo, ND 58102, USA.
FAU - Petricoin, Emanuel F
AU  - Petricoin EF
AD  - Center for Applied Proteomics and Molecular Medicine, School of Systems Biology, 
      George Mason University, Manassas, VA 20110, USA.
FAU - Goetz, Matthew P
AU  - Goetz MP
AUID- ORCID: 0000-0002-4383-270X
AD  - Departments of Oncology and Pharmacology, Mayo Clinic Breast Cancer Specialized 
      Program of Research Excellence (SPORE), Women's Cancer Program, Mayo Clinic 
      Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.
FAU - Bear, Harry D
AU  - Bear HD
AD  - Departments of Surgery and Microbiology & Immunology, Division of Surgical 
      Oncology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 
      23298, USA.
FAU - Tang, Amy H
AU  - Tang AH
AUID- ORCID: 0000-0002-5772-2878
AD  - Leroy T. Canoles Jr. Cancer Research Center, Department of Microbiology and 
      Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23501, USA.
LA  - eng
GR  - BC180907/U.S. Department of Defense/
GR  - R01 CA140550/NH/NIH HHS/United States
GR  - MF14S-009-LS/Center for Innovative Technology/
PT  - Journal Article
PT  - Review
DEP - 20200824
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7565566
OTO - NOTNLM
OT  - Cytoxan
OT  - EGFR/K-RAS/SIAH signaling pathway
OT  - and Taxotere)
OT  - chemo-resistance
OT  - clinical diagnostics
OT  - concurrent ACT regimen (Adriamycin
OT  - improved patient survival
OT  - neoadjuvant chemotherapy (NACT)
OT  - pathologic incomplete responders (pIR)
OT  - prognostics
OT  - residual cancer burden (RCB)
OT  - sequential ACT regimen (AC-T)
OT  - triple-negative breast cancer (TNBC)
OT  - tumor recurrence
OT  - tumor-driving signaling pathways in TNBC
COIS- The authors describe no conflict of interests.
EDAT- 2020/08/28 06:00
MHDA- 2020/08/28 06:01
PMCR- 2020/08/24
CRDT- 2020/08/28 06:00
PHST- 2020/07/10 00:00 [received]
PHST- 2020/08/10 00:00 [revised]
PHST- 2020/08/20 00:00 [accepted]
PHST- 2020/08/28 06:00 [entrez]
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2020/08/28 06:01 [medline]
PHST- 2020/08/24 00:00 [pmc-release]
AID - cancers12092392 [pii]
AID - cancers-12-02392 [pii]
AID - 10.3390/cancers12092392 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Aug 24;12(9):2392. doi: 10.3390/cancers12092392.