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Review
. 2020 Apr 8;12(4):916.
doi: 10.3390/cancers12040916.

The Landscape of Targeted Therapies in TNBC

Elena Vagia  1 , Devalingam Mahalingam  1 , Massimo Cristofanilli  1
Affiliations
Review

The Landscape of Targeted Therapies in TNBC

Elena Vagia et al. Cancers (Basel). .

Abstract

Triple negative breast cancer (TNBC) constitutes the most aggressive molecular subtype among breast tumors. Despite progress on the underlying tumor biology, clinical outcomes for TNBC unfortunately remain poor. The median overall survival for patients with metastatic TNBC is approximately eighteen months. Chemotherapy is the mainstay of treatment while there is a growing body of evidence that targeted therapies may be on the horizon with poly-ADP-ribose polymerase (PARP) and immune check-point inhibitors already established in the treatment paradigm of TNBC. A large number of novel therapeutic agents are being evaluated for their efficacy in TNBC. As novel therapeutics are now incorporated into clinical practice, it is clear that tumor heterogeneity and clonal evolution can result to de novo or acquired treatment resistance. As precision medicine and next generation sequencing is part of cancer diagnostics, tailored treatment approaches based on the expression of molecular markers are currently being implemented in clinical practice and clinical trial design. The scope of this review is to highlight the most relevant current knowledge regarding underlying molecular profile of TNBC and its potential application in clinical practice.

Keywords: DNA damage repair; molecular profiling; personalized medicine; targeted treatment; triple negative breast cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
When replication fork comes upon DNA SSBs, it is very likely to collapse and generate DSBs requiring the involvement of HR pathway to repair them.
Figure 2
Figure 2
Schematic of the most relevant molecular pathways and targeted agents in TNBC. Tyrosine kinase receptor is activated upon binding of growth factors leading to activation of signaling pathways. PI3K/AKT pathway and inhibitor drugs: Phosphorylated PI3K activate AKT. The activation of AKT triggers downstream protein complexes mTORC activation that initiate gene transcription and promote cell growth. AR pathway is activated in LAR subtype tumors. Platinum drugs act through DNA damaging mechanism. PARP inhibitors induce “synthetic lethality” in BRCA deficient tumors.
See this image and copyright information in PMC

References

    1. Nik-Zainal S., Davies H., Staaf J., Ramakrishna M., Glodzik D., Zou X., Martincorena I., Alexandrov L.B., Martin S., Wedge D.C., et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. 2016;534:47–54. doi: 10.1038/nature17676. - DOI - PMC - PubMed
    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019. CA Cancer J. Clin. 2019;69:7–34. doi: 10.3322/caac.21551. - DOI - PubMed
    1. Duffy M.J., McGowan P.M., Crown J. Targeted therapy for triple-negative breast cancer: Where are we? Int. J. Cancer. 2012;131:2471–2477. doi: 10.1002/ijc.27632. - DOI - PubMed
    1. Keegan T.H.M., Kurian A.W., Gali K., Tao L., Lichtensztajn D.Y., Hershman D.L., Habel L.A., Caan B.J., Gomez S.L. Racial/ethnic and socioeconomic differences in short-term breast cancer survival among women in an integrated health system. Am. J. Public Health. 2015;105:938–946. doi: 10.2105/AJPH.2014.302406. - DOI - PMC - PubMed
    1. Iwata H., Im S.-A., Masuda N., Im Y.-H., Inoue K., Rai Y., Nakamura R., Kim J.H., Hoffman J.T., Zhang K., et al. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients. J. Glob. Oncol. 2017;3:289–303. - PMC - PubMed