Targeting Cancer Stem Cells

Overview

Cancer stem cells (CSCs) are tumor-initiating cells (TICs) that produce the various differentiated progeny that make up the bulk of the rapidly dividing tumor.1,2 They represent a small subpopulation of the tumor.


diagram

CSCs are unique in that they both self-renew and generate differentiated progeny, so they retain certain features of normal stem cells, such as:

  • Ability to remain relatively quiescent
  • Expression of multidrug resistance transporters and DNA damage repair enzymes
  • Altered metabolism
  • Ability to better withstand oxidative stress
diagram

Oncogenic Expression

Efforts to identify CSC or tumor initiating cell (TIC) biomarkers have been largely unsuccessful due to overlapping expression in normal tissues.1,2

Due to the features they share with normal stem cells, CSCs may be more resistant than other tumor cells to traditional chemotherapy and radiation.3,4

  • Traditional chemotherapy and radiotherapy target the rapidly dividing differentiated bulk of the tumor but often fail to eliminate CSCs.
  • Experimentally, CSCs have demonstrated the ability to regenerate the heterogenous cell populations of the parental tumor after serial transplantations in xenograft models.

Therapeutic Potential

Inhibiting CSC function has the potential to overcome chemoresistance by blocking the tumor cell's ability to regenerate, exhausting its growth potential.

Recent technological advances, such as patient-derived xenografts (PDX) and next-generation sequencing, will allow the precise study of TICs and the identification of potential targets. The identification of CSC- or TIC-specific biomarkers may allow the targeted elimination of these cancer cells.2,4

  1. Codony-Servat J, Verlicchi A, Rosell R. Cancer stem cells in small cell lung cancer. Transl Lung Cancer Res. 2016;5(1):16-25.
  2. Codony-Servat J, Rosell R. Cancer stem cells and immunoresistance: clinical implications and solutions. Transl Lung Cancer Res. 2015;4(6):689-703.
  3. Williams SA, Anderson WC, Santaguida MT, Dylla SJ. Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century. Lab Invest. 2013;93(9):970-982.
  4. Valent P, Bonnet D, De Maria R, et al. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer. 2012;12(11):767-775.

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