The cancer stem cell hypothesis proposes that a small cell population called cancer stem cells (CSC) or tumor progenitors is responsible for tumor formation and metastasis due to its ability to self-renew, differentiate and migrate. Moreover, this population has been implicated to therapy resistance and tumor recurrence. It has been argued that the standard cancer monotherapy eliminates bulk tumor cells but not a CSC population, eventually leading to relapse. This new concept of tumorigenesis suggests that a tumor will not recur if no CSC had survived, and therapies that also target tumor progenitors may lead to more effective cancer treatments. Biomarkers that are deregulated in tumor progenitors are of special interest because they not only serve as potential targets in cancer therapy but also may be used to predict treatment outcome. The number of cancer stem cells and their intrinsic determinant of radiosensitivity vary between tumors affecting their radiocurability. Therefore, CSC-associated markers are an example of predictors for radiocurability that can be prospectively used for individualized tailoring of treatment. Emerging high throughput screening technologies employing functional cell-based approaches, comprehensive genomic and proteomic analysis expand our knowledge regarding the role of genes and proteins in the regulation of CSC properties and allow us to develop new predictive biomarkers and therapeutic strategies.

Properties of Cancer Stem Cells (CSCs): (A) Cancer stem cells have specific markers: prostate tumor cells stained with stem cell marker ALDH1A3 and marker of DNA double strand break γH2A.X; (B) CSCs are self-renewing: analysis of sphere forming properties of prostate tumor cells; arrows indicate spheres with size of more than 100 μm; (C) CSCs are multipotent: staining of breast cancer xenograft tumors with antibodies to markers CD44 and CD24 showed heterogeneous tumor cell populations; (D) CSC are tumorigenic: bioluminescence imaging of prostate xenograft tumors that express the luciferase gene; (E) CSCs are therapy resistant. (c) Anna Dubrovska

The objectives of our study are:

  • Characterization of new CSC based biomarkers for the development of predictive tests based on CSC density, distribution and sensitivity to therapy.
  • Identification of small molecules which can specifically target CSC to restore tumor radio- and chemo responsiveness.
  • Understanding the genetic programs and biological processes underlying cancer stem cell biology.