An insight into the cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer

Future Oncol. 2021 Nov;17(31):4185-4206. doi: 10.2217/fon-2021-0172. Epub 2021 Aug 3.

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.

Keywords: breast cancer; breast cancer stem cells; chemoresistance; signaling pathway; triple-negative breast cancer.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / physiology
  • Cell Survival
  • Drug Resistance, Neoplasm
  • Female
  • Hedgehog Proteins / physiology
  • Hippo Signaling Pathway
  • Humans
  • NF-kappa B / physiology
  • Neoplastic Stem Cells / drug effects*
  • Receptors, Notch / physiology
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology
  • Wnt Signaling Pathway

Substances

  • ATP-Binding Cassette Transporters
  • Hedgehog Proteins
  • NF-kappa B
  • Receptors, Notch