3.6. Conclusions. References

Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

Part I. Stem Cells

The stem cell, whether normal or cancerous, is intrinsically associated with its niche, the strong interaction between the two resulting in the niche’s control over stem cell fate. Therefore, understanding the complex interactions between CSCs and their niche microenvironments will contribute to the development of effective new treatment strategies that eliminate both the bulk of tumour cells and CSCs. The concept that the niche microenvironment might be a therapeutic target is a consistent alternative to the direct targeting of the tumour lesion.

Therapies that target CSCs may have unique properties compared to those that target the bulk of a tumour. Assuming that CSCs represent only a small proportion of an entire tumour, eradicating them might have little impact on the size of the tumour. Over time, however, the tumour can be expected to exhaust itself and dissipate, because it will have lost the capacity for long-term self-renewal (Yang and Wechsler-Reya, 2007). Therefore, successful therapeutic strategies will target the functions that all CSC niches have in common: mediating self-renewal and maintaining an undifferentiated state and CSC activity.

From a clinical perspective, it remains to be established whether such therapies are feasible. Antibodies against the fibronectin receptor VLA-4 (a4β1 integrin) and disruption of VEGFR1+ cellular cluster formation could block the metastasis of well-established tumours (Kaplan et al., 2005). Interestingly, high VLA-4 expression on leukaemia cells reduces their chemosensitivity through interaction with fibronectin in the bone marrow, resulting in a poor induction of remission and minimal residual disease (MRD) in the bone marrow, ultimately leading to recurrence and short-term survival (Matsunaga et al., 2003). Thus, the combination of CSC targeting with the use of conventional agents against tumour mass should be considered. Indeed, combinations of antiangiogenic drugs and conventional chemotherapies have proven to be more effective than either mode of therapy alone (Tozer et al., 2005), particularly because they can prevent metastasis by disrupting the interaction between CSCs and their niche.

The theory that tumours depend for their long-term growth and propagation on the interaction between a population of CSCs and their niche has profound implications for our understanding and treatment of cancer. The latest drugs targeting CSCs or their microenvironments are expected to minimize complications and, at the same time, improve patient quality of life. Thus, from both scientific and clinical perspectives, the biology of stem cells and their respective niches is one of the most promising fields of research for understanding and targeting cancer.


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