Cancer stem cell studies could open the door to personalized, targeted treatments for brain cancers

(Reprinted from ‘Sick Kids’, 4 June 2009. University Hospital Toronto, Canada)

Scientists in Toronto and in the United Kingdom have developed a new technique to efficiently grow Cancer Stem Cells in the lab.

The scientists obtained tissue samples from gliomas donated by recently-diagnosed patients. Using these samples, they developed a technique that enables Cancer Stem Cells to grow in cultures, while maintaining their “purity” (preserving the characteristics of the stem cells and preventing them from mutating as they grow).

The researchers used an adherent cell culture technique. This involves taking stem cells from the original tumour and growing them in a single layer on a surface coated with laminin.

“The increased efficiency in developing these stem cell lines gives us the opportunity to test targeted therapies on each patient’s individual tumour and hopefully feed the treatment back to the patient within a few months of diagnosis. This is the Holy Grail,” …adding that it would take several years for scientists to reach the point of creating individualized treatment on a patient-by-patient basis.
The new research is the first step in the process.

Cancer Stem Cells

Cancer Stem Cells (CSCs) are cancer cells (found within solid tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients.

CSCs appear to represent a very small proportion of the tumor. this may not necessarily select for drugs that act specifically on the stem cells. It seems possible conventional chemotherapies kill mainly other cancer cells, which form the bulk of the tumor. Some CSCs, which gave rise to the cancer could remain untouched and be responsible for a relapse of the disease.

Drug finds chink in armor of Cancer Stem Cells

RARE but pernicious Cancer “Stem” Cells, blamed for the spread and invincibility of some tumours, may be more vulnerable than we thought.

The suggestion is that a small number of such cells within tumours may be the precursors to the other cancer cells in those tumours.  The stem cells may also be resistant to ordinary cancer drugs, allowing the cancer to recur.

To hunt for drugs that target these cells, Piyush Gupta, a molecular biologist at the Broad Institute at the Massachusetts Institute of Technology, and colleagues genetically engineered ordinary human cells so that they acquired some of the properties of Cancer Stem Cells, including being impervious
to chemotherapy.

Next they tested thousands of different compounds for their ability to kill these reprogrammed cells.  One called salinomycin stood out because it killed the reprogrammed cells, but not healthy cells, and was easy to obtain in large quantities.  When Gupta’s team added salinomycin to cultured human breast-cancer cells, it was about 100 times as effective at killing the Cancer Stem Cells as the popular anti-cancer drug, paclitaxel.  What’s more, mice injected with human breast-cancer cells developed fewer aggressive tumours when treated with salinomycin compared with paclitaxel.

Little is known about the drug’s safety, or whether it would find its way through the human bloodstream to tumours.  But it does prove that Cancer Stem Cells aren’t invincible, Gupta says.

(Reprinted from New Scientist 22 August 2009)