Emerging Intrinsic Therapeutic Targets for Metastatic Breast Cancer
Abstract
Simple Summary
Abstract
1. Introduction
2. Current Management of Breast Cancer
3. Tumor Intrinsic Targeting
3.1. Targeting CDK4 and CDK6 in Breast Cancer
3.2. Targeting the PI3K/AKT/mTOR Pathway in Breast Cancer
3.3. Inhibiting PARP in TNBC
3.4. Targeting TROP-2 in Breast Cancer
3.5. Targeting Src Kinases in Breast Cancer
3.6. Targeting the IL-6/JAK/STAT Pathway in Breast Cancer
3.7. Histone Deacetylase Inhibitors for Breast Cancer
3.8. Inhibition of EGFR/HER2
3.9. Targeting Insulin/IGF1R Signaling in mBC
3.10. Breast Cancer Stem-Cell-Targeted Therapies
3.11. Androgen Receptor
3.12. Matrix Metalloproteinases and Angiogenesis Inhibitors
3.13. Immunotherapy of Breast Cancer
3.14. Antisense Oligonucleotide Strategy as a Future Therapy for Breast Cancer Treatment
4. Concluding Remarks
Targets | Targeted Agents | Patient Population | FDA Approval Year | Reference | ||
---|---|---|---|---|---|---|
Generic Name | Brand Name | Class | ||||
TROP-2 | Sacituzumab govitecan (-hziy) | Trodelvy | TROP-2 ADC | TNBC mBC | 2021 | [93] |
HR+, HER2− mBC | 2023 | [96] | ||||
CDK4 and CDK6 | Palbociclib | Ibrance | CDK4/CDK6 inhibitor | HR+, HER2− mBC | 2017 | [32] |
Ribociclib | Kisqali | CDK4/CDK6 inhibitor | HR+, HER2− mBC | 2017 | [32] | |
Abemaciclib | Verzenio | CDK4/CDK6 inhibitor | HR+, HER2− mBC | 2017 | [32] | |
PI3K/AKT/mTOR pathway | Alpelisib | Piqray | PI3K inhibitor | PIK3CA-mutated, HR+, HER2− mBC | 2019 | [53] |
Buparlisib | PI3K inhibitor | PIK3CA-mutated, HR+, HER2− mBC | [55,56] | |||
Pictilisib | PI3K inhibitor | PIK3CA-mutated, ER+, HER2− mBC | [57] | |||
Taselisib | PI3K inhibitor | PIK3CA-mutated, ER+, HER2− mBC | [58] | |||
Everolimus | Afinitor | mTOR inhibitor | HR+, HER2− mBC | 2012 | [65] | |
Dactolisib | PI3K-mTOR inhibitor | N/A | [68] | |||
Perifosine | AKT inhibitor | mBC | [202] | |||
PARP | Olaparib | Lynparza | PARP inhibitor | Germline BRCA mutations mBC | 2022 | [72] |
Talazoparib | Talzenna | PARP inhibitor | Germline BRCA mutations mBC | 2018 | [74] | |
Veliparib | PARP inhibitor | Metastatic TNBC | [78] | |||
Src pathway | Saracatinib | Src inhibitor | HR− mBC | [115] | ||
Dasatinib | Sprycel | Src inhibitor | mBC | [118] | ||
Bosutinib | Bosulif | Src inhibitor | mBC | [120] | ||
Histone deacetylase | Entinostat (MS-275) | Histone deacetylase inhibitor | N/A | [143,144] | ||
Vorinostat (SAHA) | Histone deacetylase inhibitor | N/A | [145,146] | |||
Panobinostat (LBH-589) | Farydak | histone deacetylase inhibitor | N/A | [147,148] | ||
HER2 | Trastuzumab | Herceptin | HER2 antibody | HER2+ mBC | 1998 | [18] |
Pertuzumab | Perjeta | HER2 antibody | HER2+ mBC | 2017 | [21] | |
Neratinib | Nerlynx | HER2 small-molecule inhibitor | HER2+ mBC | 2020 | [24] | |
Lapatinib | HER2 small-molecule inhibitor | HER2+ mBC | 2007 | [154] | ||
Pyrotinib | HER2 small-molecule inhibitor | HER2+ mBC | [156,158] | |||
BCSCs | γ-Secretase inhibitors (GSIs) | γ-secretase small-molecule inhibitor | N/A | [190] | ||
Diethylamino benzaldehyde (DEAB) | ALDH inhibitor | N/A | [207] | |||
AR | Enzalutamide | Xtandi | AR inhibitor | AR+ TNBC | [224] | |
Bicalutamide | Casodex | AR inhibitor | AR+, ER+ | [219] | ||
Insulin/IGF1R pathway | Xentuzumab | IGF antibody | HR+, HER2− mBC | [163] | ||
Ganitumab | IGF1R antibody | HR+ mBC | [165] | |||
MMP | Marimastat | MMP pan-inhibitor | mBC | [229] | ||
Angiogenesis | Bevacizumab | Avastin | VEGF-A antibody | mBC | 2008 (revoked 2011) | [267] |
Ramucirumab | Cyramza | VEGFR-2 antibody | mBC | [268] | ||
ICIs | Atezolizumab | Tecentriq | PD-L1 antibody | mTNBC | 2019 (withdrawn 2021) | [250] |
Pembrolizumab | Keytruda | PD-1 antibody | mTNBC | 2020 | [255] |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ADC | antibody–drug conjugate |
ADP | poly-adenosine diphosphate |
AI | aromatase inhibitor |
AON | antisense oligonucleotide |
APCL | adenomatous polyposis coli protein-like gene |
AR | androgen receptor |
ATM | ataxia telangiectasia mutated gene |
ATRA | all-trans retinoic acid |
BCSC | breast cancer stem cell |
BRCA1 | breast cancer susceptibility gene 1 |
BRCA2 | breast cancer susceptibility gene 2 |
CAR-T | chimeric antigen receptor (CAR) T-cell |
CSA | Cockayne syndrome group A |
CSC | cancer stem cell |
CTLA-4 | cytotoxic T-lymphocyte-associated antigen 4 |
DEAB | diethylamino benzaldehyde |
DHEAS | dehydroepiandrosterone sulfate |
DHT | 5α-dihydrotestosterone |
DLL-1 | Delta-like-1 |
DLL-3 | Delta-like-3 |
DLL-4 | Delta-like-4 |
EGF | epidermal growth factor |
EGFR | epidermal growth factor receptor |
EMA | European Medicine Agency |
EMT | epithelial-to-mesenchymal transition |
ER | estrogen receptor |
ER− | ER-negative |
ER+ | ER-positive |
ESR1 | estrogen receptor gene |
FDA | The United States Food and Drug Administration |
GFR | growth factor receptor |
GSI | γ-secretase inhibitor |
HDACi | histone deacetylase inhibitor |
HDAC | histone deacetylase |
HER2 | human epidermal growth factor receptor 2 |
HER2− | HER2-negative |
HER2+ | HER2-positive |
Hh | Hedgehog |
HR | hormone receptor |
HR+ | HR-positive |
ICI | immune checkpoint inhibitor |
iDFS | invasive disease-free survival |
IL-6 | cytokine interleukin-6 |
InsR | insulin receptor |
JAK | Janus kinase |
mBC | advanced or metastatic breast cancer |
MMP | matrix metalloproteinase |
mTOR | mammalian target of rapamycin |
N/A | not applicable |
NRARP | Notch-regulated ankyrin repeat protein |
OS | overall survival |
p110 | the catalytic subunit of PI3K |
p85 | the regulatory subunit of PI3K |
PARP | poly-adenosine diphosphate-ribose polymerase |
PD-1 | programmed cell death-1 |
PD-L1 | programmed cell death ligand-1 |
PFS | progression-free survival |
PI3K | phosphoinositide 3 kinase |
PR | progesterone receptor |
pRB | retinoblastoma protein |
RB | retinoblastoma |
RTK | growth factor receptor tyrosine kinase |
SFK | Src family kinase |
STAT | signal transducers and activators of transcription |
TNBC | triple-negative breast cancer |
TROP-2 | trophoblast cell-surface antigen 2 |
ZIP9 | iron-regulated transporter-like protein 9 |
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Li, J.; Goh, E.L.K.; He, J.; Li, Y.; Fan, Z.; Yu, Z.; Yuan, P.; Liu, D.-X. Emerging Intrinsic Therapeutic Targets for Metastatic Breast Cancer. Biology 2023, 12, 697. https://doi.org/10.3390/biology12050697
Li J, Goh ELK, He J, Li Y, Fan Z, Yu Z, Yuan P, Liu D-X. Emerging Intrinsic Therapeutic Targets for Metastatic Breast Cancer. Biology. 2023; 12(5):697. https://doi.org/10.3390/biology12050697
Chicago/Turabian StyleLi, Jiawei, Eyleen L. K. Goh, Ji He, Yan Li, Zhimin Fan, Zhigang Yu, Peng Yuan, and Dong-Xu Liu. 2023. "Emerging Intrinsic Therapeutic Targets for Metastatic Breast Cancer" Biology 12, no. 5: 697. https://doi.org/10.3390/biology12050697
APA StyleLi, J., Goh, E. L. K., He, J., Li, Y., Fan, Z., Yu, Z., Yuan, P., & Liu, D.-X. (2023). Emerging Intrinsic Therapeutic Targets for Metastatic Breast Cancer. Biology, 12(5), 697. https://doi.org/10.3390/biology12050697