Cancer Stem Cells and Tumor Microenvironment in Radiotherapy

Chapter
Part of the Cancer Treatment and Research book series (CTAR)

Abstract

Ionizing radiation (IR) began to be a powerful medical modality soon after Wilhelm Röntgen’s discovery of X-rays in 1895. Today about 60% of cancer patients worldwide receive radiotherapy in their course of cancer control. In the past decades, the technology for precisely delivering tumor IR dose such as stereotactic body radiation therapy (SBRT) has been significantly enhanced, which increases the overall local tumor response and clinical benefit. However, in achieving the goal for long-term cancer control, radiotherapy (RT) has faced several major challenges including the elucidation of the microenvironment causing tumor repopulation and resistance, especially with the most aggressive tumor cells in late phase metastatic lesions. To meet this challenge, a great deal of effort has been devoted to revealing not only the mechanistic insight of tumor heterogeneity, but also the emerging complexity of the irradiated microenvironment. Such new knowledge provides the explanation for the long recognized tumor heterogeneity and tumor cell repopulation, one the major “R”s in tumor radiobiology, which involves cancer stem cells (also termed tumor-imitating cells, cancer stem-like cells, or stem like cancer cells). It is generally accepted that CSCs plays a key role in tumor adaptive radioresistance and are involved in clinical tumor response. The specific cell surface biomarkers as well as the biological topographies of CSCs in many solid tumors have been identified; some of them overlap with those detected in normal stem cells. However, the exact molecular mechanism causing the radioresistant phenotype of CSCs, especially the dynamic nature of CSCs themselves under RT and their communication with the irradiated tumor microenvironment including stromal cells and immune cells, remains to be elucidated. Further elucidation of the complexity of the irradiated local tumor microenvironment in which CSCs reside may generate significant new information to resensitize radioresistant tumor cells and thus to improve therapeutic efficacy. In this chapter, I will describe the general information on normal stem cells, CSCs, CSCs-associated tumor repopulation and energy reprogramming and potential therapeutic targets. The dynamic features of radioresistance-associated factors such as NF-κB and HER2 in some CSCs including breast cancer and GBM will be discussed.

Keywords

Tumor resistance Radiotherapy Microenvironment Cancer stem cells Tumor repopulation Metabolic reprogramming Immunoresponse Radiosensitization 

Abbreviations

ALDH

Aldehyde dehydrogenase

ATRA

All-trans retinoic acid

ATP

Adenosine triphosphate

BCSCs

Breast cancer stem cells

CDK1

Cyclin-dependent kinases 1

CDK2

Cyclin-dependent kinases 2

CHK1

Checkpoint kinase 1

Chk1

Checkpoint kinase 1

CSCs

Cancer stem cells

CXCR4

Chemokine C-X-C motif receptor 4

EMT

Epithelial–mesenchymal transition

ESCs

Embryonic stem cells

FAO

Fatty acid oxidation

FIR

Fractionated ionizing radiation

FR

Fractionated radiation

GBM

Glioblastoma multiforme

GSCs

Glioblastoma multiforme stem cells

HIF-1α

Hypoxia inducible factor alpha

HSCs

Hematopoietic stem cells

ICD

IR-induced immunogenic cell death

iPSCs

Induced pluripotent stem cells

IR

Ionizing radiation

ICD

IR-induced immunogenic cell death

LDH

Lactate dehydrogenase

NF-κB

Nuclear factor kappa B

NSCs

Normal stem cells; neural stem cells

MnSOD

Manganese-containing superoxide dismutase

ROS

Reactive oxygen species

SBRT

Stereotactic body radiation therapy

OXPHOS

Oxidative phosphorylation

RT

Radiation therapy

TNBC

Triple-negative breast cancer

Notes

Acknowledgements

I regret not being able to cite all the important work done in this area due to space restrictions. I’d like to take this opportunity to thank the invaluable input and discussions from all of my colleagues, collaborators and friends who contributed many novel concepts to my research. I thank the graduate students, postdoctoral fellows, and lab personnel who have been involved in the research projects and performed the major of research work in my lab. The author also acknowledges grant support from the National Institutes of Health RO1 CA133402 and CA152313.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Radiation Oncology, School of MedicineNCI-Designated Comprehensive Cancer Center, University of California DavisSacramentoUSA

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