Triple negative breast cancer: Emerging therapeutic modalities and novel combination therapies. (January 2018)

• Record Type: Journal Article
• Authors: Lee, Alice; Djamgoz, Mustafa B.A.
• Is Part Of: Cancer treatment reviews. Volume 62(2018)
• Page Start: 110
• Page End: 122
• Publication Date: 2018-01
• Subjects: Triple-negative breast cancer -- Targeted therapy -- Combination therapy -- Biomarkers; Cancer -- Periodicals; Cancer -- Treatment -- Periodicals; Neoplasms -- therapy -- Periodicals; Cancer -- Périodiques; Cancer -- Traitement -- Périodiques; Cancer -- Treatment; Electronic journals; Periodicals; 616.99406
• DOI: 10.1016/j.ctrv.2017.11.003
• Languages: English
• ISSNs: 0305-7372

Abstract

Highlights: TNBC is a heterogeneous disease which is clinically difficult to manage. Lack of licensed targeted therapies has encouraged the search for novel targets. Drugs inhibiting PARP1, tyrosine kinases and immune-checkpoints are in clinical trials. Emerging targets include the β-adrenergic receptor and voltage-gated sodium channel. Novel drug combinations and predictive biomarkers promise to improve treatment. Abstract: Triple negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer which lacks oestrogen receptors, progesterone receptors and HER2 amplification, thereby making it difficult to target therapeutically. In addition, TNBC has the highest rates of metastatic disease and the poorest overall survival of all breast cancer subtypes. Resultantly, development of targeted therapies for TNBC is urgently needed. Recent efforts aimed at molecular characterisation of TNBCs have revealed various emerging therapeutic targets including PARP1, receptor and non-receptor tyrosine kinases, immune-checkpoints, androgen receptor and epigenetic proteins. Key successes include that of the PARP inhibitor, olaparib, which prolonged progression-free survival in a trial of BRCA -mutated breast cancer and for which clinical approval (in this setting) appears imminent. Nevertheless, the heterogeneity of TNBC has limited the clinical benefits of many trialled therapies in 'unselected' patients. Further, drug resistance develops following use of many targeted monotherapies due to upregulation of compensatory signalling pathways. In this review, we evaluate the current status of investigational targeted treatments and present evidence for the role of novel biomarkers and combination therapies in increasing response rates and circumventing drug-induced resistance. Additionally, we discuss promising novel targets in metastatic TNBC identified through preclinical and/or epidemiological studies.