Determinants of resistance to chemotherapy and ionizing radiation in breast cancer stem cells

Cancer Lett. 2016 Oct 1;380(2):485-493. doi: 10.1016/j.canlet.2016.07.018. Epub 2016 Jul 19.


Breast cancer cells are suggested to be organized in a hierarchical manner with a subpopulation of stem cells, termed as breast cancer stem cells (BCSCs), which contribute significantly to tumorigenesis, cancer recurrence and metastasis. BCSCs have been demonstrated to exhibit significant resistance to conventional chemo- and radiotherapy. Recent evidence suggests that treatment of breast cancers with radiation or chemotherapy agents induces stem cell-like properties in non-stem cells. Herein, we provide an overview of the key determinants of resistance to chemotherapy and radiation in BCSCs. To this end and by the use of bioinformatics, the molecular pathways, the defining markers, as well as the microenvironmental and genetic factors, which are implicated in the maintenance of stemness, chemo- and radioresistance in BCSCs, are identified and presented. Our findings could provide the foundation for the design of targeted chemo- or radiotherapeutic regimens in order to eliminate or sensitize BCSCs to cytotoxic therapies and prevent tumor relapse and metastasis.

Keywords: Bioinformatics; Breast cancer stem cells; Chemoresistance; Chemotherapy; Radioresistance; Radiotherapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Computational Biology
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Gene Regulatory Networks
  • Humans
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / radiation effects*
  • Phenotype
  • Protein Interaction Maps
  • Radiation Tolerance* / genetics
  • Risk Factors
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Tumor Microenvironment


  • Antineoplastic Agents
  • Biomarkers, Tumor