Abstract
Since their description and identification in leukemias and solid tumors, cancer stem cells (CSC) have been the subject of intensive research in translational oncology. Indeed, recent advances have led to the identification of CSC markers, CSC targets, and the preclinical and clinical evaluation of the CSC-eradicating (curative) potential of various drugs. However, although diverse CSC markers and targets have been identified, several questions remain, such as the origin and evolution of CSC, mechanisms underlying resistance of CSC against various targeted drugs, and the biochemical basis and function of stroma cell-CSC interactions in the so-called ‘stem cell niche.’ Additional aspects that have to be taken into account when considering CSC elimination as primary treatment-goal are the genomic plasticity and extensive subclone formation of CSC. Notably, various cell fractions with different combinations of molecular aberrations and varying proliferative potential may display CSC function in a given neoplasm, and the related molecular complexity of the genome in CSC subsets is considered to contribute essentially to disease evolution and acquired drug resistance. In the current article, we discuss new developments in the field of CSC research and whether these new concepts can be exploited in clinical practice in the future.
Highlights
The principle concept of cancer stem cells (CSC) has gained increasing acceptance in recent years [1,2,3,4,5,6,7,8,9,10]
Oncogenic signaling is considered to derive from three distinct classes of molecules, i) the driver lesions that are often disease-specific or at least disease-related, like BCR/ABL in chronic myeloid leukemia (CML), ii) broadly expressed mutated oncogenic kinases, and iii) cytokine-activated stem cell kinases that play a role in survival or/and growth of neoplastic stem cells (NSC)
Can we translate the CSC concept into clinical practice? Most of the conventional anti-cancer agents currently used in daily practice or in clinical trials are primarily acting on rapidly dividing cells that make up the bulk of the tumor, whereas most CSC
Summary
Cancer stem cells in basic science and in translational oncology: can we translate into clinical application?. Axel Schulenburg1,2,7*, Katharina Blatt, Sabine Cerny-Reiterer, Irina Sadovnik, Harald Herrmann, Brigitte Marian, Thomas W Grunt, Christoph C Zielinski and Peter Valent
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