An Insight Into the Cancer Stem Cell Survival Pathways Involved in Chemoresistance in Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is the most complex, aggressive and fatal subtype of breast cancer. Owing to the lack of targeted therapy and heterogenic nature of TNBC, chemotherapy remains the sole treatment option for TNBC, with taxanes and anthracyclines representing the general chemotherapeutic regimen in TNBC therapy. But unfortunately, patients develop resistance to the existing chemotherapeutic regimen, resulting in approximately 90% treatment failure. Breast cancer stem cells (BCSCs) are one of the major causes for the development of chemoresistance in TNBC patients. After surviving the chemotherapy damage, the presence of BCSCs results in relapse and recurrence of TNBC. Several pathways are known to regulate BCSCs’ survival, such as the Wnt/β-catenin, Hedgehog, JAK/STAT and HIPPO pathways. Therefore it is imperative to target these pathways in the context of eliminating chemoresistance. In this review we will discuss the novel strategies and various preclinical and clinical studies to give an insight into overcoming TNBC chemoresistance. We present a detailed account of recent studies carried out that open an exciting perspective in relation to the mechanisms of chemoresistance.

Graphical Abstract

Keywords:

• breast cancer
• breast cancer stem cells
• chemoresistance
• signaling pathway
• triple-negative breast cancer

Author contributions

M Mir and N Wani initiated the study, designed the plan and edited the manuscript. H Qayoom and M Mir wrote the manuscript and designed the figures and tables. M Mir, B Alshehri and H Qayoom reviewed the manuscript and arranged the references. M Mir, B Alshehri and N Wani read and approved the final manuscript.

Acknowledgments

The authors are thankful to the University Grants Commission (UGC) Govt. of India, New Delhi and University of Kashmir, Srinagar for their support.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors are thankful to the University Grants Commission (UGC) Govt. of India, New Delhi and University of Kashmir, Srinagar for their support