The Niche

Drug screening on cancer stem cells

A recent Cell paper by Priyush Gupta, Rob Weinberg, Eric Lander and other researchers from the Broad and MIT reports a potential way to kill the cancer cells that really matter.

Here is A screen for cancer killers from NatureNews (quotes from University of Toronto’s John Dick, others)

Here is New screening for more potent cancer drugs in the New York Times. (quotes from Stanford’s Mike Clarke, others)

Cancer stem cells are cells capable of growing malignant tumours anew, and there is a surfeit of controversy about whether this is an elite subpopulation or the majority of cells in the tumour. (See Cancer stem cells, becoming common)

The researchers manipulated immortalized cancer stem cells and were able to sort out a subpopulation that resembles cancer stem cells, then they were able to identify drug that selectively kills the cancer stem cells. That’s a big deal, as a growing body of evidence indicates that the cells best able to cause a tumour to regrow are also particularly able to resist cancer drugs. (See Cancer stem cells resemble healthy ones, resist chemotherapy)

Two questions come to mind:

1) How well do these cells represent cancer stem cells? (See Careful assays for cancer stem cells )

2) Will compounds that kill cancer stem cells also kill healthy stem cells? (See How breast cancer resists treatment )

Here’s a nice summary from Jane Visvader, a breast cancer stem cell expert at the The Walter and Eliza Hall Institute of Medical Research.

This is an elegant demonstration of the power of using high throughput screening to target resistant cancer cell subsets. The authors have shown that they can specifically target mesenchymal-like cells in breast tumors, found to be resistant to a standard chemotherapeutic agent (Paclitaxel), using salinomycin.

Here’s this from Piyush Gupta, which addresses whether the cells act like bona fide cancer stem cells

The gist: Cancer stem cells have been difficult to study because they

cannot be maintained as pure populations in culture. Passage through

an EMT has been recently reported (by the Weinberg groups) to induce a

significant increase in the proportion of stem-like epithelial cells.

We show that passage through an EMT also confers increased drug

resistance to cells. Using genetic vectors to induce an EMT, it was

possible to induce a stable increase in the proportion of stem-like

cells. We then performed a chemical screen to find compounds that were

specifically toxic to cells that had passed through an EMT. Compounds

that were identified in this way were then tested the identified

compounds on cancer cell lines that we had not genetically

manipulated, to determine if they acted on bona fide cancer stem cells.

Why the study is of interest:

Cancer stem cells are resistant to many forms of death-inducing

insults. This has suggested that it may be difficult to find therapies

that specifically target CSCs. Our study shows that it is possible to

find agents that selectively kill cancer stem cells and provides a

general method for doing so.

Caveats and further experiments:

Further study will be needed to determine if the chemical we

identified, salinomycin, can be used in patients. In such studies, the

long-term effects on normal stem cell biology will also need to be



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