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Cancer stem cell study finds genetic 'root' of disease

19 May 2014
Appeared in BioNews 754

Definitive support for the existence of human cancer stem cells has been found, according to researchers at the University of Oxford and the Karolinska Institutet in Sweden.

Cancer stem cells (CSCs) are a type of cancer cell that have the ability to give rise to all the cell types within a tumour. CSCs are thought to form the 'root' of the cancer and are responsible for driving its growth and evolution. Their existence, however, has been debated for decades by the scientific community, as clear evidence of their appearance in human cancers has so far been lacking.

'We have identified a subset of cancer cells [and] shown that these rare cells are invariably the cells in which the cancer originates', said study author Dr Petter Woll, from the University of Oxford. 'It suggests that if you want to cure patients, you would need to target and remove these cells at the root of the cancer'.

Scientists investigated 15 patients with myelodysplastic syndromes, where the bone marrow does not make enough healthy blood cells. Over time, MDS can develop into a form of leukaemia called acute myeloid leukaemia (AML) through an accumulation of specific genetic mutations.

The researchers took samples of the patients' bone marrow at several points during the progression of the disease and identified cancerous cells. By analysing genetic changes, they were able to track the origin of mutations leading to cancer cell formation. They found a subset of MDS cells that showed the distinctive markers of stem cells, which they identified as CSCs as they were the only cell type that was able to fully reproduce a tumour, supporting the theory that they function as 'roots'.

Current cancer treatments, like chemotherapy, aim to reduce the overall size of the tumour. Chemotherapy attacks the cells that form the bulk of the tumour, but might not reach the smaller population of CSCs, which could then regenerate the tumour and cause a relapse of the disease.

'It's like having dandelions in your lawn. You can pull out as many as you want, but if you don't get the roots they'll come back,' explained Dr Woll.

CSCs have been found in a number of human cancers to date, but the findings have remained controversial as the lab tests used in their identification were thought to be unreliable.

'In our studies, we avoided the problem of unreliable lab tests by tracking the origin and development of cancer-driving mutations in MDS patients', said study lead Professor Jacobsen.

The results are promising but should be interpreted with caution as these results are limited to the MDS and might not be applicable to other forms of cancer. Dr Woll noted: 'We can't offer patients today new treatments with this knowledge. What it does is give us a target for the development of more efficient and cancer stem cell specific therapies to eliminate the cancer'.

First evidence of cancer stem cells brings hope for possible future treatment
The Independent |  15 May 2014
Found: Cancer's deadly 'mother cells' that if killed, could wipe out the disease
Daily Mail |  16 May 2014
Genetic tracking identifies cancer stem cells in patients
University of Oxford (press release) |  16 May 2014
Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo
Cancer Cell |  15 May 2014
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CommentGenetic Roots of Cancers and Mechanisms of Cancer Drug Resistance ( - 02/01/2015)
Some types of cancer run in families, but most are not clearly linked to genetics. Cancer is such a common disease that it is no surprise that many families have at least a few members who have had cancer. Unfortunately, cancer researchers continue to view cancer as the result of an accumulation of a large number of individual genetic mutations. According to Cancer Research UK, all cancers develop because something has gone wrong with one or more of the genes in a cell. But most of these gene changes happen during our lives. They happen as we get older or because of something we are exposed to, such as cigarette smoke or sunlight. We each have about 25,000 genes. So far scientists have found around 300 that play some part in the development of cancer. The Father of Oncology says that cancerous cells are iron-overloaded (iron-rich, iron-saturated) cells. Cancer is a single disease with a single cause. At the cellular level, cancer occurs when cellular iron overload affects cellular organelles. Chromosomes are structures within the nucleus that are made up of DNA. Cellular iron overload often affects DNA and chromosomes, creates genome chaos. Typically, cancers are categorized according to the tissue in which they originated. Pancreatic cancer - local/regional iron overload in pancreatic tissues; lung cancer - local/regional iron overload in lung tissues. Local/regional iron overload can be inherited or acquired. Primary tumors always develop at body sites of excessive iron deposits. Such deposits can be inherited from parents or can be acquired during life. Iron disorders are inherited and can be confirmed with genetic testing. Genes that maintain iron homeostasis may facilitate iron uptake, storage or egress, or the regulation of any of these processes. Why cancer genes don’t always cause cancer? Iron-deficiency genes or/and iron-deficiency events can neutralize cancer genes. Clinical iron-deficiency methods and direct intratumoral injections of iron-deficiency agents can eliminate inoperable tumors and metastases; can successfully overcome cancer drug resistance.
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