Cancer Stem Cells : Revival Targeted


American Association of Cancer Research defines cancer Stem Cells (CSCs) as cells within a tumour which possess capacity to self-renew and to cause heterogeneous lineages of cancer cells that comprise the tumour. These cells exhibit the properties of stem cells and are tumorigenic. They are said to cause the revival of cancers after treatment with conventional methods such as chemotherapy.

Solutions like chemotherapy target only the bulk of the tumour and have certain side-effects but not the metastatic CSCs which constitute only about 1 to 3% of all cells in a tumour. The CSCs can further divide and differentiate to cause relapse of the tumour.

Photo credits: Peter Znamensky
Photo credits: Peter Znamensky

Brief history of the debate over CSCs

Rudolf Virchow, the German pathologist proposed in 1855 that cancers arise from activation of dormant, embryonic-like cells present in mature tissue. He argued that cancerous cells must originate from living cells. In 1997, Bonnet and Dick isolated a subpopulation of leukaemic cells that expressed a specific surface marker CD34, but lacked CD38 capable of initiating tumours in mice histologically similar to the donor (a person suffering from acute myeloid leukaemia).

Further researchers like Reya et al. 2001 and Dean et al. 2005 postulated the cancer stem cell hypothesis. According to it, the malignant part of a tumour actually arises from an adult stem cell. An ‘adult stem cell gone bad’ and a  ‘more differentiated cell that has regained stem cell abilities’ remain the controversial contenders as the initiators of tumours (Gupta et al. 2009; Rosen and Jordan 2009; Schatton et al. 2009). In some tumours, prostrate cancers for example, the origin of tumour was, in most likelihood, a normal adult stem cell that has escaped the control of its niche (Wang et al. 2009).

Implications on cancer treatment

Present techniques like chemotherapy target only a fraction, the fully differentiated and the differentiating cells, of the tumour and even often target normal cells. Techniques that mark cancer cells fail to mark the undifferentiated CSCs. Advances in cancer treatment have substantially decreased the mortality rate due almost all cancers but miserably failed to avoid revival of cancers in the affected patients.

Drugs or techniques against cancer, not unlike other diseases, are first tested on animal models like mice. While these model organisms may be good for testing the protocol but not much can be learned of the revival of a disease due to their short life spans. Mice live only for a couple of years but the cancer revival figures are studied for five year intervals. If attempts at developing markers specific to CSCs succeed, the revival rate of all cancers would hit rock bottom.

But for that to happen, we need to enhance our understanding of how cells differentiate, how they learn to stop differentiating and why they sometimes forget what they learn.

Checkpoint

CSCs can differentiate into heterogeneous lineages. It is safe to assume that maybe more than one lineages of CSCs exist themselves of which only one is in significant numbers. Even if we develop a marker for a particular lineage of CSCs in case of a particular tumour, maybe one of the other lineages of CSCs grows to significant number to further differentiate. That would cause revival of histologically same but molecularly different tumour.

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