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Review
. 2015 Mar 12:3:257-75.
doi: 10.1016/j.bbacli.2015.03.003. eCollection 2015 Jun.

The fate of chemoresistance in triple negative breast cancer (TNBC)

Elma A O'Reilly  1 , Luke Gubbins  2 , Shiva Sharma  1 , Riona Tully  2 , Matthew Ho Zhing Guang  2 , Karolina Weiner-Gorzel  2 , John McCaffrey  3 , Michele Harrison  4 , Fiona Furlong  5 , Malcolm Kell  6 , Amanda McCann  2
Affiliations
Review

The fate of chemoresistance in triple negative breast cancer (TNBC)

Elma A O'Reilly et al. BBA Clin. .

Abstract

Background: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype.

Scope of review: How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed.

Major conclusions: Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome.

General significance: Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy.

Keywords: Cellular fates; Cellular senescence; Chemoresistance; Hypoxia; Triple negative breast cancer (TNBC).

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Figures

Fig. 1
Fig. 1
Mechanisms of Chemoresistance in TNBC. (A) ABC transporters efflux chemotherapeutics out of cancer cells (B) Overexpression of β-tubulin III subunit induces paclitaxel resistance (C) Mutations in DNA repair enzymes and enzymes altering drug sensitivity (D) Alterations in genes involved in apoptosis prevent chemotherapy-induced apoptosis (E) ALDH1 and glutathione (GSH)/Glutathione-S-transferase (GST) mediate chemotherapeutic inactivation/detoxification (F) Role of NF-ϰB signaling pathway in chemoresistance.
Fig. 2
Fig. 2
The role hypoxia plays in cellular fates including references.
See this image and copyright information in PMC

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