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Method seeks better cancer drugs

14th August 2009

A new generation of anticancer drugs, whose advent may bring an entirely new cancer treatment scheme, is the subject of controversial US research.

cancercell

The drugs involved would have a special ability to kill cancer stem cells, the same cells many scientists believe fuel the growth of tumours.

Cancer stem cells are still mainly a theoretical construct, but this may change with the advent of the new drug screening method.

It is not currently understood why these so-called cancerous stem cells are so resistant to the usual cancer treatments, but they are often difficult to locate within the body.

Chemotherapy can kill up to 99% of the cancerous cells in a tumour, but some scientists believe that self-regenerating cancer stem cells are the source of all cancers.

In order to conduct their research, scientists at the Broad Institute and the Massachusetts Institute of Technology in the US managed to genetically engineer breast cancer stem cells that do not develop past the stem cell state.

Lead author Piyush Gupta said that there is a lot of evidence to suggest that these cells are responsible for many of the recurrences that are observed after treatment has stopped.

The research team said that 32 of 16,000 screened molecules were able to specifically target and destroy cancer stem cells.

Although none of the chemicals has been proved to be effective against cancer, one had already received approval as an anti-cancer drug.

Yet another approach to fighting cancer stem cells focuses on the use of antibodies.

If this emerging class of anti-cancer drugs can be developed, one option would be to use them in combination with chemotherapy.

Gupta said that doctors could probably lower chemotherapy doses if they were using a combination of drugs that attacked specific types of cells.

Eric S. Lander, director of the Broad Institute, said that there is a Pyrrhic victory when manufacturers make drugs that kill 99.9% of the cells in a tumour but fail to kill the 0.1% that causes problems.

He said that the new anti-cancer drugs could mean a renaissance in cancer therapeutics.

In recent years, cancer stem cells have been discovered for all types of tumours, including brain, prostate, and breast tumours.

However, some cancer scientists do not believe that cancer stem cells exist.

Bert Vogelstein, a leading cancer geneticist at Johns Hopkins University, said that the cancer stem cell hypothesis has already been challenged on many fronts, and that a paper on melanomas last year showed that 100% of melanoma cancer cells were cancer stem cells.

He said that if a significant portion of the cells belonging to a tumour are cancer stem cells, then existing chemotherapy agents are already capable of killing such cells.

However, Gupta's team believes that using standard chemotherapy measures in conjunction with new drugs targeting cancer stem cells is the best possible strategy, since mature cancer cells may possess the ability to turn themselves back into cancer stem cells.

Robert Weinberg, a leading cancer biologist at M.I.T. and co-author said that the non-stem cells in a tumour may regenerate new stem cells.

But Vogelstein said that there was no difference between stem cells and the bulk cancer cells in solid tumours, and a screen for drugs to kill melanoma cells was by definition also going to kill the melanoma cancer stem cells.

He said that, because most of the compounds in use were now clearly not doing the job, novel methods for screening could be extremely valuable.


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