The fate of chemoresistance in triple negative breast cancer

BBA Clin. 2015 Mar 12;3:257-75. doi: 10.1016/j.bbacli.2015.03.003. eCollection 2015.

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

O'Reilly EA1, Gubbins L2, Sharma S1, Tully R2, Guang MH2, Weiner-Gorzel K2, McCaffrey J3, Harrison M4, Furlong F5, Kell M6, McCann A2.

Author information

• 1UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of Medicine and Medical Science (SMMS), Belfield, Dublin 4, Ireland ; Department of Surgery, Mater Misericordiae Hospital, Dublin 7, Ireland.
• 2UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of Medicine and Medical Science (SMMS), Belfield, Dublin 4, Ireland.
• 3Department of Oncology, Mater Misericordiae Hospital, Dublin 7, Ireland.
• 4Department of Pathology, Mater Misericordiae Hospital, Dublin 7, Ireland.
• 5School of Pharmacy, Queens University Belfast, Belfast BT7 1NN, UK.
• 6Department of Surgery, Mater Misericordiae Hospital, Dublin 7, Ireland.

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.