Targeting Therapies for Cancer Stem Cells

  • Manash K. Paul
  • Vijay R. Marati
  • Yuvaraj Sambandam
  • Lurdes Queimado
  • Gautam Chaudhuri
  • Ilangovan Ramachandran
  • R. Ileng KumaranEmail author


Cancer stem cells (CSCs) represent a small subpopulation of the bulk of a tumor. The CSCs possess the characteristics of self-renewal, clonal repopulation and resistance to conventional therapies, and thereby contribute to cancer metastasis and relapse. Moreover, CSCs establish homeostasis under stress via autophagy, endoplasmic reticulum (ER)-stress-mediated unfolded protein response (UPR) pathways, and mitophagy. Recent evidence indicate that besides many protein molecules, the noncoding RNAs (ncRNAs) also play a significant role in CSC growth and maintenance, as well as in cancer metastasis and therapeutic resistance. Therefore, targeting the CSCs has evolved as an important strategy for cancer therapy. Recent advancements in cancer immunotherapy has shown excellent application of its potential in targeting CSCs. Various immunotherapy approaches like immune checkpoint inhibitors, dendritic cell (DC)-based vaccines, adoptive T-cell therapy, oncolytic viruses, and combination therapies are currently used to target the CSCs. Also, recent multi-omic technologies can divulge exclusive CSC-associated cell surface markers, which can be used in detection or therapeutics of CSCs for various cancers. Additionally, detection of CSC-specific neoantigens can help in the design of new immunotherapeutics for cancers. Available literature suggests that many types of cancers have CSCs located in anatomically distinct niches within the tumor microenvironment (TME), which help in CSC’s survival and maintenance. Unique pro-survival and anti-survival intercellular and intracellular cross talk also exists among the CSCs, its niche and/or TME. Modulating unique CSC-niche/TME interaction(s) can reduce the maintenance potential of CSCs, and thereby prevent tumor development and progression or cancer metastasis. Many important cell signaling pathways play a key role in the maintenance and regulation of CSCs. Several new potential therapeutic molecules that could specifically target the CSCs or their signaling pathways to overcome cancer metastasis, treatment-resistance or relapse, are being developed. Furthermore, the emerging clinical studies strongly support the use of drugs as a monotherapy or in combination with other available standard therapies. This chapter highlights the roles of various critical CSC markers and pathways in or around the CSCs, and the several CSC-targeting approaches or therapies that are used or being developed to treat cancer for a cure.


Noncoding RNAs Unfolded protein response (UPR) Endoplasmic reticulum (ER) stress Autophagy Cancer stem cells (CSCs) Immunotherapy Dendritic cell (DC)-based vaccine Adoptive immunotherapy Oncolytic virotherapy Combination chemotherapy CSC cell surface markers CSC-associated tumor microenvironment CSC signaling pathway Hedgehog Notch Wnt/β-catenin 



Our sincere appreciation to Dr. Satish Ramalingam (Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kanchipuram, Tamil Nadu, India) for his helpful discussion, carefully reading this book chapter and providing critical comments.

Conflict of Interest

The authors declare no conflict of interest.


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Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Manash K. Paul
    • 1
  • Vijay R. Marati
    • 2
  • Yuvaraj Sambandam
    • 3
  • Lurdes Queimado
    • 4
    • 5
    • 6
  • Gautam Chaudhuri
    • 7
  • Ilangovan Ramachandran
    • 8
    • 7
  • R. Ileng Kumaran
    • 9
    Email author
  1. 1.Division of Pulmonary and Critical Care Medicine, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA
  2. 2.Independent Consultant Medical WritingTucsonUSA
  3. 3.Immune Monitoring Core, Comprehensive Transplant Center, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  4. 4.Department of Otorhinolaryngology – Head and Neck SurgeryThe University of Oklahoma Health Sciences CenterOklahoma CityUSA
  5. 5.Department of Cell BiologyThe University of Oklahoma Health Sciences CenterOklahoma CityUSA
  6. 6.Department of PediatricsThe University of Oklahoma Health Sciences CenterOklahoma CityUSA
  7. 7.Department of Obstetrics and Gynecology, David Geffen School of MedicineUniversity of California at Los AngelesLos AngelesUSA
  8. 8.Department of Endocrinology, Dr. ALM PG Institute of Basic Medical SciencesUniversity of Madras, Taramani CampusChennaiIndia
  9. 9.Biology DepartmentFarmingdale State CollegeFarmingdaleUSA

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