Triple negative breast cancer: Emerging therapeutic modalities and novel combination therapies.

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.

• Authors: Alice Lee, Mustafa B A Djamgoz
• Journal: Cancer treatment reviews (Cancer Treat Rev) Vol. 62 Pg. 110-122 (Jan 2018) ISSN: 1532-1967 [Electronic] Netherlands
• PMID: 29202431 (Publication Type: Journal Article, Review)
• Copyright: Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Adrenergic beta-Antagonists
• Androgen Receptor Antagonists
• Angiogenesis Inhibitors
• Antineoplastic Agents, Immunological
• Histone Deacetylase Inhibitors
• Poly(ADP-ribose) Polymerase Inhibitors
• Protein Kinase Inhibitors

Topics

• Adrenergic beta-Antagonists (therapeutic use)
• Androgen Receptor Antagonists (therapeutic use)
• Angiogenesis Inhibitors (therapeutic use)
• Antineoplastic Agents, Immunological (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma (drug therapy)
• Histone Deacetylase Inhibitors (therapeutic use)
• Humans
• Poly(ADP-ribose) Polymerase Inhibitors (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Triple Negative Breast Neoplasms (drug therapy)