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Leukemia Stem Cell Drug Discovery

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Part of the Methods in Molecular Biology book series (MIMB,volume 2185)

Abstract

The relative survival of cancer patients, when considering the tumoral stage at diagnosis, has not changed significantly in the last three decades, in spite of our increasingly detailed knowledge of the molecular alterations occurring in human tumors. In parallel, despite a growing number of clinical trials being conducted, the absolute number of drugs that are effective in humans is declining, and many new drugs move into the market without having enough evidence of their benefit on survival or quality of life. In part, this failure is due to the discordance between the results from preclinical and clinical trial phases, therefore leading to a high percentage of apparently promising lead compounds being abandoned in the transfer to the clinic. This discordance is caused, to a large degree, by the use of inappropriate animal models in the first stages of drug development. In this chapter, we discuss how the development of cancer therapies needs to be redesigned in order to achieve cancer cure, and how this redesign must involve the generation of better animal models, based on the tenets of the cancer stem cell theory, and capable of recapitulating all the aspects of human cancer. The use of such improved models should increase the likelihood of success in drug development, reducing the number of agents that go into trial, and the amount of patients undergoing useless trials.

Key words

  • Leukemic stem cells
  • Cancer stem cells
  • Epigenetic reprogramming
  • Leukemia
  • Animal models

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  • DOI: 10.1007/978-1-0716-0810-4_3
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Acknowledgements

Research at CC’s laboratory was partially supported by FEDER, EU, MINECO (SAF2017-83061-R), the “Fundación Ramón Areces,” a Research Contract with the “Fundación Síndrome de Wolf-Hirschhorn o 4p-,” and institutional grants from the “Fundación Ramón Areces” and “Banco de Santander” to the CBMSO. Research in ISG group is partially supported by FEDER and by SAF2015-64420-R MINECO/FEDER, UE, RTI2018-093314-B-I00 MCIU/AEI/FEDER,UE, by Junta de Castilla y León (UIC-017, CSI001U16, and CSI234P18), by The German Carreras Foundation (DJCLS 02R/2016 and DJCLS 07R_2019), by the German Federal Office for Radiation Protection (BfS)-Germany (FKZ: 3618S32274), and by the Fundacion Unoentrecienmil (CUNINA project). ISG lab is a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program.

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Correspondence to César Cobaleda .

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Cobaleda, C., Sánchez-García, I. (2021). Leukemia Stem Cell Drug Discovery. In: Cobaleda, C., Sánchez-García, I. (eds) Leukemia Stem Cells. Methods in Molecular Biology, vol 2185. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0810-4_3

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  • DOI: https://doi.org/10.1007/978-1-0716-0810-4_3

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0809-8

  • Online ISBN: 978-1-0716-0810-4

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