Drug repurposing towards targeting cancer stem cells in pediatric brain tumors

Abstract

In the pediatric population, brain tumors represent the most commonly diagnosed solid neoplasms and the leading cause of cancer-related deaths globally. They include low-grade gliomas (LGGs), medulloblastomas (MBs), and other embryonal, ependymal, and neuroectodermal tumors. The mainstay of treatment for most brain tumors includes surgical intervention, radiation therapy, and chemotherapy. However, resistance to conventional therapy is widespread, which contributes to the high mortality rates reported and lack of improvement in patient survival despite advancement in therapeutic research. This has been attributed to the presence of a subpopulation of cells, known as cancer stem cells (CSCs), which reside within the tumor bulk and maintain self-renewal and recurrence potential of the tumor. An emerging promising approach that enables identifying novel therapeutic strategies to target CSCs and overcome therapy resistance is drug repurposing or repositioning. This is based on using previously approved drugs with known pharmacokinetic and pharmacodynamic characteristics for indications other than their traditional ones, like cancer. In this review, we provide a synopsis of the drug repurposing methodologies that have been used in pediatric brain tumors, and we argue how this selective compilation of approaches, with a focus on CSC targeting, could elevate drug repurposing to the next level.

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Acknowledgments

We would like to thank all members in Dr. Abou-Kheir’s Laboratory (The WAK Lab) and Dr. Abou-Antoun’s Laboratory for their help on this work.

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WAK and TAA conceived the concept and idea of the present review. HFB, TAA, and WAK worked on the study design strategy and selected the topics to be discussed. HFB and MKE did literature searches and screened titles and abstracts for relevance. HFB, MKE, TEZ, and JB abstracted the data from the eligible full text articles, analyzed and interpreted the data, and drafted the manuscript. TAA and WAK critically revised the manuscript with input from the entire team. All authors have read and approved the final draft.

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Correspondence to Tamara Abou-Antoun or Wassim Abou-Kheir.

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Bahmad, H.F., Elajami, M.K., El Zarif, T. et al. Drug repurposing towards targeting cancer stem cells in pediatric brain tumors. Cancer Metastasis Rev 39, 127–148 (2020). https://doi.org/10.1007/s10555-019-09840-2

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Keywords

  • Drug repurposing
  • Cancer stem cells
  • Pediatric brain tumors
  • Low-grade glioma
  • Medulloblastoma