Recent advances in the development of novel anti-cancer drugs targeting cancer stem/progenitor cells

Murielle Mimeault, Surinder K. Batra

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

Recent advances in basic and clinical oncology have led to the identification and characterization of several deregulated gene products involved in cancer progression to invasive, metastatic, and recurrent disease stages. Particularly, an emerging body of experimental evidence has revealed that an accumulation of genetic and/or epigenetic alterations can lead to the malignant transformation of tissue-resident adult stem/progenitor cells into leukemic or tumorigenic cancer stem/progenitor cells. These immature cancer cells endowed with a self-renewal capacity and aberrant differentiation potential that can drive leukemia and tumor development and metastases being responsible for treatment resistance and disease relapse. Therefore, the molecular targeting of deregulated signaling elements that may contribute to the uncontrolled growth, survival, invasion, and resistance of these cancer-initiating cells to current clinical cancer therapies is of great therapeutic interest. Potential anticancer drug targets include telomerase, anti-apoptotic factors, DNA repair, and detoxifying enzymes and ATP-binding cassette multidrug transporters as well as distinct oncogenic cascades, including hedgehog, EGFR, Wnt/b-catenin, Notch, and/or polycomb group (PcG) protein chromatin-silencing pathways. The combined targeting of these deregulated gene products should reverse multidrug resistance and eliminate the cancer-initiating cells and their differentiated progenies. Hence, these novel targeting approaches could be used to improve the efficacy of current therapeutic treatments against the highly aggressive, metastatic, recurrent and lethal cancers.

Original languageEnglish (US)
Pages (from-to)415-430
Number of pages16
JournalDrug Development Research
Volume69
Issue number7
DOIs
StatePublished - Nov 2008

Keywords

  • Anti-cancer drugs
  • Cancer stem/progenitor cells
  • Combination therapy
  • Drug resistance
  • Metastases
  • Molecular targeting
  • Tumor growth

ASJC Scopus subject areas

  • Drug Discovery

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