Therapeutic Strategies for Metastatic Triple-Negative Breast Cancers: From Negative to Positive
Abstract
:1. Background
2. Molecular Subtypes of TNBC
3. Current FDA Approved Treatment Options
3.1. Alterations of DNA Damage Signaling Pathway and Targeted Therapeutics
3.2. Immune Therapies in TNBC Patients
3.3. Antibody–Drug Conjugates (ADC) as a Targeted Therapy
4. Promising Treatment Options with Drugs That Need FDA Approval
4.1. Antibody–Drug Conjugates (ADC)
4.2. Signaling Pathway-Targeted Therapies
5. Walking Forward
6. Limitations
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ADC | antibody–drug conjugate |
AR | androgen receptor |
CBR | clinical benefit rate |
CR | complete response |
ctDNA | circulating tumor DNA |
CPS | combines positive score |
CTC | circulating tumor cells |
CTLA4 | cytotoxic T-lymphocyte-associated protein 4 |
DCR | disease control rate |
DFS | disease-free survival |
ER | estrogen receptor |
HR | homologous recombination |
HR | hazard ratio |
HER2 | epidermal growth factor receptor 2 |
ITT | intention to treat |
IL | interleukin |
NGS | next-generation sequencing |
ORR | objective response rate |
OS | overall survival |
PARP | poly (ADP ribose) polymerase |
PR | progesterone receptor |
PR | partial response |
PD-1 | programmed cell death protein 1 |
PD-L1/2 | programmed death-ligand 1/2 |
PFS | progression-free survival |
TNBC | triple-negative breast cancer |
VEGF | vascular endothelial growth factor |
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Name of the Drug(s) | Target | Patients Types | Clinical Trial Number |
---|---|---|---|
Ladiratuzumab vedotin (LV) | Zinc transporter LIV1 conjugated with MMAE | Advanced or metastatic TNBC | NCT01969643 |
LV plus pembrolizumab | LIV1 and PD-1 | Front line therapy in TNBC patient | NCT03310957 |
NBE-002 | ROR1 conjugated with anthracycline | Advanced solid tumors, including TNBC | NCT044410099 |
Trastuzumab deruxtecan | HER2 conjugated with topoisomerase1 inhibitor | HER2-low un-resectable and/or metastatic breast cancer | NCT03734029 |
Ipataserib (GDC-0068) (LOTUS trial) | AKT | PI3K-AKT activated TNBC | NCT02162719 |
Ipataserib (GDC-0068) plus atezolizumab | AKT and PD-L1 | Locally advanced unresectable or metastatic triple-negative breast cancer | NCT04177108 |
Capivasertib (AZD5363) (PAKT trial) | AKT | Advanced or metastatic TNBC | NCT02423603 |
Alpelisib | P110 alpha (catalytic subunit of PI3K) | Advanced TNBC | NCT04251533 |
Bicalutamide | Androgen receptor | Metastatic TNBC | NCT00468715 |
Enzalutamide | Androgen receptor | Advanced, androgen receptor-positive, TNBC | NCT01889238 |
Bicalutamide plus palbociclib | Androgen receptor and CDK4/6 | AR(+) metastatic breast cancer, including TNBC | NCT02605486 |
Bicalutamide plus ribociclib | Androgen receptor and CDK4/6 | AR(+) TNBC | NCT03090165 |
AZD8186 (single agent) and AZD8186 plus abiraterone acetate | PI3K beta/delta and androgen receptor | TNBC | NCT01884285 |
Avastin plus everolimus | VEGF and mTORC1 | Locally advanced TNBC with tumors predicted insensitive to standard chemotherapy | NCT02456857 |
Avastin | VEGF | Metastatic TNBC | NCT03577743 |
Avastin plus atezolizumab | VEGF and PD-L1 | Metastatic TNBC | NCT04739670 |
Azacitidine plus entinostat | DNA methyltransferase and HDAC | Advanced breast cancers including TNBC | NCT01349959 |
Lurbinectedin | RNA polymerase II | Metastatic breast cancer, pancreatic cancer, and metastatic colorectal cancer | NCT02210364 |
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Nandini, D.; Jennifer, A.; Pradip, D. Therapeutic Strategies for Metastatic Triple-Negative Breast Cancers: From Negative to Positive. Pharmaceuticals 2021, 14, 455. https://doi.org/10.3390/ph14050455
Nandini D, Jennifer A, Pradip D. Therapeutic Strategies for Metastatic Triple-Negative Breast Cancers: From Negative to Positive. Pharmaceuticals. 2021; 14(5):455. https://doi.org/10.3390/ph14050455
Chicago/Turabian StyleNandini, Dey, Aske Jennifer, and De Pradip. 2021. "Therapeutic Strategies for Metastatic Triple-Negative Breast Cancers: From Negative to Positive" Pharmaceuticals 14, no. 5: 455. https://doi.org/10.3390/ph14050455