Radiation resistance in breast cancer: are CD44+/CD24-/proteosome low/PKH26+ cells to blame?

Identification and characterization of cancer-initiating cells (CICs) enriched for stem cell-like functions and the establishment of a link between CICs and tumor recurrence, chemotherapy resistance and radiation resistance, and metastasis have been the focus of cancer research for the last eight years. Although this field has its share of controversies, it is becoming apparent that cells isolated from recurrent or residual tumors or both are enriched for cancer cells that have a specific phenotype compared with heterogeneous cells in the primary tumor. Enrichment of CICs in tumors subjected to radiation therapy could be due in part to the delivery of sublethal doses of treatment and the efficient radical scavenging system within CICs. Sublethal doses of radiation are sufficient to induce senescence of non-CICs while forcing CICs to gain several new properties related to cell cycle progression in addition to maintaining or enhancing stem cell characteristics of pre-treatment CICs. Characterizing pathways responsible for the increase in CICs after therapy and exploiting the unique characteristics of therapy-resistant CICs for developing targeted therapies are becoming a central focus of research in the rapidly evolving field of CICs.