Radiation Resistant Cancer Stem Cells

Michelle Bae
June 19, 2017

Submitted as coursework for PH241, Stanford University, Winter 2017

Background on Radiation Therapy for Cancer

Fig. 1: Distinction between cancer stem cell targeted (above) and conventional (below) cancer therapies. (Source: Wikimedia Commons)

Radiation therapy has been an important part of cancer treatment. More than half of cancer patients will be treated with radiation for at least part of their treatment. [1] Ionizing radiation, which forms ions in the cells it passes through, is particularly used for cancer treatment because it can effectively shrink tumors in the tissues it goes through. It does so by damaging the DNA of cancer cells or killing them to prevent them from growing and dividing any more. [1]

Radiation Resistant Cancer Stem Cells

Cancer stem cells (CSCs) are small population of cells found within tumors that have similar characteristics to those of normal stem cells. These almost immortal cells can self-renew and differentiate into multiple cell types, which makes them very tumorigenic and metastatic. [2] Unfortunately, research shows evidence that CSCs are inherently resistant to radiation. [3] This is found to be due to their higher production level of antioxidant proteins, which increases their resistance against ionizing radiation. [4] There is a high chance that some CSCs survive even after radiation has killed most cancer cells, and these remaining cells can repopulate the tumor and cause cancer recurrence. Because of their tumorigenic nature, CSCs can be good targets for cancer treatment. It is hypothesized that selectively targeting and eliminating them may prevent metastasis and cancer relapse, thus possibly overcoming the current limitations of radiation therapy. [5] Fig. 1 illustrates the distinction between cancer stem cell targeted and conventional cancer therapies. Therapies aiming to eliminate CSCs include targeting surface biomarkers, signaling pathways that regulate CSC self-renewal and differentiation, using drug-efflux pumps involved in apoptosis resistance, providing microenvironmental signals that prevent CSC growth, manipulating miRNA expression, and inducing CSC apoptosis and differentiation. [5]

Improving Radiation Therapy for Cancer Treatment

The efficacy of radiation treatment can be enhanced based upon recent research on CSCs. Radiotherapy can currently cure patients suffering from localized cancers but often fails against systemic disease, mostly because it does not target CSCs that lead to cancer relapse. [3] Traditional radiation therapy is not precise enough for individual treatment, and it should be improved so that the treatment planning strategy involves specific targeting based on predictive markers. [3] These predictive markers should obviously include CSC markers, as these markers may change the way radiation is delivered. [3]

© Michelle Bae. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.


[1] "Radiation Therapy Principles," American Cancer Society, September 2011.

[2] J. P. Medema, "Cancer Stem Cells: The Challenges Ahead," Nat. Cell Biol. 15, 338 (2013).

[3] F. Pajonk, E. Vlashi, and W. H. McBride, "Radiation Resistance of Cancer Stem Cells: The 4 R's of Radiobiology Revisited," Stem Cells 28, 639 (2010).

[4] S. Ali, "Radiation Oncology: Mechanism and Resistance," Physics 241, Stanford University, Winter 2012.

[5] D. L. Dragu et. al., "Therapies Targeting Cancer Stem Cells: Current Trends and Future Challenges," World J. Stem Cells 7, 1185 (2015).