| Stem Cells and Cancer |
| Sunday, 13 January 2008 | |
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Brynn Kvinlaug reveals the role of stem cells in cancer Stem cells frequently feature in the media as potential cures for degenerative diseases. As cells with infinite capabilities to divide and differentiate into new cell types, they may eventually be used to regenerate tissues and organs. When mutated however, stem cells also seem to play a role in cancer, able to develop into entire tumours if even a few cells are present. Cancer stem cells may soon change how we identify and treat the disease, becoming a new target in the battle to find an effective cancer cure. Have you ever experienced difficulty removing a dandelion from your garden? Repeatedly, the weed is cut at its stem—only to resurface a short time later, time and time again. In a final attempt to rid the garden of its nuisance, the roots are dug out, but even a minute portion remaining can enable the weed to grow back with a vengeance. The root cells that allow this regeneration can be likened to a specific group of cells within tumours, termed cancer stem cells (CSCs). Normal stem cells are vital to the body, serving to provide new populations of cells for growth and repair. CSCs have similar characteristics to normal stem cells, but with mutations that give them the dangerous ability to reform tumours if not removed from the body. Despite improvements to the early detection and treatment of cancer, current therapies are limited by their ability to cure the disease completely. Common methods of cancer treatment such as radiotherapy, chemotherapy and surgery all target and reduce the tumour mass as a whole. These treatments are extremely toxic and non-specific, destroying not only the susceptible tumour cells, but also healthy neighbouring cells. Despite such toxic treatments, complications frequently arise where tumour cells survive, the tumour reappears. Current evidence suggests that it is in fact CSCs at the core of tumour formation. Even if nearly all the tumour mass is removed, a few remaining CSCs may therefore be all that is necessary for cancer to recur. CSCs were first identified in patients with acute myeloid leukaemia, but since then they have also been identified in solid tumours in the breast, brain, other organs. In the healthy state, each of these organs is comprised of the mature, differentiated, short-lived cell types characteristic of the tissue. The mature cells are replenished by long-lived stem cells unique to the organ. Through a tightly regulated process, each stem cell has the ability either to form another stem cell through self-renewal, or to differentiate into the progenitor cells that give rise to the mature cell types of that tissue. These daughter progenitor cells are more restricted in their lineage choice and divide frequently. To date, several factors have been found to have a role in controlling the self-renewal of haematopoietic stem cells (HSCs)—stem cells of the blood. These factors include specialized proteins involved in gene transcription, as well as molecular signalling pathways within the cells. In leukaemia, mutation of this tightly regulated process occurs and the self-renewal of the stem cell becomes deregulated. This may then lead to its development into a CSC. Other research suggests that mature cells may even acquire the ability to revert back to a stem cell-like state. However, as most biological pathways and features are still the same between normal stem cells and CSCs, it is very difficult to target CSCs specifically with medical intervention. The few unique differences that do exist may be the only means of eradicating the CSC population, while sparing normal and healthy stem cells. Until recently, no differences had been found between normal and leukaemic self-renewal pathways to exploit for therapeutic purposes. However, last year, two groups demonstrated that the removal of a protein called the phosphatase and tensin homologue (PTEN) gave rise to differentiation changes of HSCs and the subsequent development of leukaemia. PTEN normally works in the cell by terminating the positive growth signals that promote cell proliferation. Inactivation of PTEN could therefore lead to increased growth signalling and thus transformation into a CSC. Other research has found that CSCs in breast tumours have different types of protein molecules on their surface from normal breast stem cells. Such differences between healthy and cancerous stem cells will need to be exploited in the development of new therapies if better prognoses are to be achieved. Another consequence of the discovery of CSCs is that the tumour mass is no longer viewed as a homogeneous entity. Current evidence suggests that a small group of CSCs amongst the other cells of blood and solid tumours are specifically responsible for tumour growth and resistance to therapeutic agents. For example, these cells can contain more membrane efflux pumps compared to normal stem cells. These pumps are capable of pumping chemotherapeutic drugs back out of the cell, making CSCs more resistant to treatment. Other mechanisms that CSCs adopt even include alterations to their cell cycle and activation of DNA repair mechanisms, protecting them from radiotherapy. Although no CSC specific drugs have reached clinical trials, it is only a matter of time until our understanding of these destructive cells improves. Targeting these cells directly may hold the key to effectively treating cancer. Just as the garden weed is tackled, to truly eradicate cancer, tumours must be pulled out at their roots. Brynn Kvinlaug is a PhD student at the Cambridge Institute for Medical Research |
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