Targeted Therapeutic Strategies for Triple-Negative Breast Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Nov 15

PMID 34778045

Citations 43

Authors

Ying Li

Zhijun Zhan

Xuemin Yin

Shujun Fu

Xiyun Deng

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, which is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR) expression and the absence of human epidermal growth factor receptor 2 (HER2) expression/amplification. Conventional chemotherapy is the mainstay of systemic treatment for TNBC. However, lack of molecular targeted therapies and poor prognosis of TNBC patients have prompted a great effort to discover effective targets for improving the clinical outcomes. For now, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi's) and immune checkpoint inhibitors have been approved for the treatment of TNBC. Moreover, agents that target signal transduction, angiogenesis, epigenetic modifications, and cell cycle are under active preclinical or clinical investigations. In this review, we highlight the current major developments in targeted therapies of TNBC, with some descriptions about their (dis)advantages and future perspectives.

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References

Hsu J, Hung M . The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer. Cancer Metastasis Rev. 2016; 35(4):575-588. PMC: 5215954. DOI: 10.1007/s10555-016-9649-6. View

Keenan T, Tolaney S . Role of Immunotherapy in Triple-Negative Breast Cancer. J Natl Compr Canc Netw. 2020; 18(4):479-489. DOI: 10.6004/jnccn.2020.7554. View

Yang X, FERGUSON A, Nass S, Phillips D, Butash K, Wang S . Transcriptional activation of estrogen receptor alpha in human breast cancer cells by histone deacetylase inhibition. Cancer Res. 2001; 60(24):6890-4. View

Esteller M, Silva J, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E . Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000; 92(7):564-9. DOI: 10.1093/jnci/92.7.564. View

Wilson C, Ramos L, Villasenor M, Anders K, Press M, Clarke K . Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat Genet. 1999; 21(2):236-40. DOI: 10.1038/6029. View

Furtado C, Luciano M, da Silva Santos R, Furtado G, Moraes M, Pessoa C . Epidrugs: targeting epigenetic marks in cancer treatment. Epigenetics. 2019; 14(12):1164-1176. PMC: 6791710. DOI: 10.1080/15592294.2019.1640546. View

Dawson M, Kouzarides T . Cancer epigenetics: from mechanism to therapy. Cell. 2012; 150(1):12-27. DOI: 10.1016/j.cell.2012.06.013. View

Anderhub S, Mak G, Gurden M, Faisal A, Drosopoulos K, Walsh K . High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers. Mol Cancer Ther. 2019; 18(10):1696-1707. DOI: 10.1158/1535-7163.MCT-18-1203. View

Malumbres M, Barbacid M . Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009; 9(3):153-66. DOI: 10.1038/nrc2602. View

10.

Costa-Pinheiro P, Montezuma D, Henrique R, Jeronimo C . Diagnostic and prognostic epigenetic biomarkers in cancer. Epigenomics. 2015; 7(6):1003-15. DOI: 10.2217/epi.15.56. View

11.

Schmid P, Adams S, Rugo H, Schneeweiss A, Barrios C, Iwata H . Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018; 379(22):2108-2121. DOI: 10.1056/NEJMoa1809615. View

12.

Brufsky A, Valero V, Tiangco B, Dakhil S, Brize A, Rugo H . Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial. Breast Cancer Res Treat. 2012; 133(3):1067-75. DOI: 10.1007/s10549-012-2008-6. View

13.

Cameron D, Brown J, Dent R, Jackisch C, Mackey J, Pivot X . Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013; 14(10):933-42. DOI: 10.1016/S1470-2045(13)70335-8. View

14.

Thomssen C, Pierga J, Pritchard K, Biganzoli L, Cortes-Funes H, Petrakova K . First-line bevacizumab-containing therapy for triple-negative breast cancer: analysis of 585 patients treated in the ATHENA study. Oncology. 2012; 82(4):218-27. DOI: 10.1159/000336892. View

15.

Wolf D, Yau C, Sanil A, Glas A, Petricoin E, Wulfkuhle J . DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial. NPJ Breast Cancer. 2017; 3:31. PMC: 5572474. DOI: 10.1038/s41523-017-0025-7. View

16.

Lee J, Hays J, Chiou V, Annunziata C, Swisher E, Harrell M . Phase I/Ib study of olaparib and carboplatin in women with triple negative breast cancer. Oncotarget. 2017; 8(45):79175-79187. PMC: 5668030. DOI: 10.18632/oncotarget.16577. View

17.

Birrer M, Moore K, Betella I, Bates R . Antibody-Drug Conjugate-Based Therapeutics: State of the Science. J Natl Cancer Inst. 2019; 111(6):538-549. DOI: 10.1093/jnci/djz035. View

18.

Ashworth A . A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol. 2008; 26(22):3785-90. DOI: 10.1200/JCO.2008.16.0812. View

19.

Cortes J, Cescon D, Rugo H, Nowecki Z, Im S, Yusof M . Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020; 396(10265):1817-1828. DOI: 10.1016/S0140-6736(20)32531-9. View

20.

Hortobagyi G, Stemmer S, Burris H, Yap Y, Sonke G, Paluch-Shimon S . Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016; 375(18):1738-1748. DOI: 10.1056/NEJMoa1609709. View