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Targeting cancer stem cells could be a powerful way to beat cancer in the future (Image from the Cancer Research UK LRI EM Unit)

Targeting cancer stem cells could be a powerful way to beat cancer in the future (Image from the Cancer Research UK LRI EM Unit)

It’s always exciting to see headlines about scientific breakthroughs, and today is no exception – we have “Breakthrough found to kill cancer spread”, “Scientists make breakthrough in fight against deadliest cancer cells” and the ambitious “Cancer – The end?

The headlines came after researchers in Boston, US, discovered a way to target cancer stem cells – the rogue cells that are believed to be at the heart of many cancers, which are resistant to radiotherapy and current chemotherapy drugs. Their results are published today in the journal Cell.

But what’s the story behind the headlines? And is this really ‘the end for cancer’?

What are cancer stem cells?
We’ve got a longer post here explaining more about cancer stem cells, and research into them.   Briefly, cancer stem cells are rare ‘immortal’ cells that are found in a number of different cancers, including breast, bowel and prostate cancer, and leukaemia.  They produce not only ‘normal’ cancer cells that go on to divide many times, forming the bulk of the tumour – but also make new cancer stem cells.

Although they’re elusive, many researchers think cancer stem cells are the driving force behind many cancers.  Certainly, they’re resistant to radiotherapy and chemotherapy. The theory goes that these treatments kill off the ‘normal’ tumour cells but don’t touch the stem cells. Eventually these start growing again and the cancer comes back.

Although the importance  – and in some cases existence  – of cancer stem cells is still a hotly-debated topic in research, there is a growing body of evidence to suggest that rogue stem cells may play a role in at least a proportion of cancers.

Many researchers around the world – including several funded by Cancer Research UK – are working on the challenge of cancer stem cells. And now Piyush Gupta and his colleagues in the States have made an important scientific breakthrough, throwing the door open to exciting future treatments for cancer.

What did they do?
It’s very difficult to work with ‘real life’ cancer stem cells, as they only make up a tiny fraction of cells in a given tumour, so are tricky to extract from tumour samples.

So the researchers developed a technique for growing immortal – but non-cancerous – human breast cells in the lab, and then used genetic engineering to give them the properties of cancer stem cells. This meant that they could grow stem cell-like cancer cells in thousands of tiny plastic dishes.

The next step was to expose these cells to thousands of different chemical compounds, to find ones that killed them.  To start with, the scientists studied around 16,000 compounds, including those from commercial chemical ‘libraries’ as well as extracts from natural sources. Just 32 of these killed the stem cell-like cells. And, of these, only four worked consistently.

Narrowing it down further, the researchers found that one chemical – an agricultural antibiotic called salinomycin – was particularly selective and effective at killing off the stem cells.  Further tests in the lab showed that salinomycin was over a hundred-fold more effective at killing cancer stem cells than paclitaxel – a commonly-used breast cancer drug.

Tests with mice transplanted with human breast cancer cells revealed that salinomycin was effective at reducing the levels of stem cells in the tumours, and reduced the chances of the cancer spreading around the body.

Is salinomycin the ‘cure for cancer’?
We need to stress that these were laboratory experiments, and there is no evidence yet that salinomycin can treat cancer in humans.  Salinomycin is currently used as an antibiotic for chickens and cows, and it can be toxic or even fatal to humans, causing serious muscle and heart problems.

There’s still a long way to go before salinomycin is tested in cancer patients, and we would not recommend anybody to take salinomycin as a treatment for cancer.  More research needs to be done to find out if it works on human tumours in the body, and if a safe dose can be given.

It may even be the case that salinomycin itself never makes it to the clinic. Quite often researchers need to tweak the chemical formula of a promising compound to make it safe or effective, and this can take time. Or there are serious side effects that mean that it’s unsafe for general use.

So why is this research so important?
Scientifically speaking, this is really good stuff.  This is the first time that researchers have found a compound that acts on cancer stem cells. This tells us that they are not entirely invincible after all, and there is hope for future treatments that can kill off stem cells as well as the ‘bulk’ of the tumour.

But  – perhaps more importantly – researchers have now discovered a way to test thousands of chemicals for activity against cancer stem cells. So even if salinomycin doesn’t turn out to be suitable for use in cancer patients, we now have a technique that can be used to discover further drugs that might be.

This research is unlikely to lead to a ‘magic bullet’ for all cancers. The role of stem cells in cancer is still not crystal clear, and although there’s evidence they play a role in many types of cancer, they’re not always implicated. And this research has only been done using stem cells ‘manufactured’ in the lab from breast cells, so we don’t yet know if it will apply to ‘real life’ cancer stem cells – or to other types of cancer.

Regardless of the caveats, today’s story is still very good news for the field of cancer research, and we look forward to seeing further significant moves forward in cancer stem cell research – and treatment – in the future.

Kat

Further reading


Reference:
Gupta, P. et al. (2009). Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening Cell DOI: 10.1016/j.cell.2009.06.034

Comments

Jo Brodie August 21, 2009

Thanks for the further explanation Kat – and hooray for robots :)

Alexey August 19, 2009

Very nicely written explanation of “dream team’s” findings.
I don’t see much breakthrough here IMHO. Cancer stem cell-like cell lines widely used before for testing new anti-cancer therapies. Some “cancer stem cell lines” even available commercially – Celprogen sell some of them.
http://www.celprogen.com/
Many researchers warn that work which done on cancer stem cell lines could very very artificial (especially in this Cell paper case) and very far from reality.

To me this methodological paper is one of examples how you sell technologies from academia to Biotech (Novartis right across the road of Broad Institute) or BigPharma. Methodology should be picked up by them and commercialized in “cancer stem cell -based screening microchip”.

Kat Arney August 17, 2009

Hi Jo,
Without going into too much detail, the researchers grew many thousands of little ‘pools’ of breast cells in plastic dishes (384-well, if you’re interested). These were epithelial (lining) cells, which had been made ‘immortal’ by infecting them with a virus. The researchers then genetically engineered the cells using a technique called RNA interference, reducing the activity of a gene called E-cadherin. This causes the cells to change, becoming very similar in nature to cancer stem cells. Further lab tests showed that they were – to all intents and purposes – almost identical to breast cancer stem cells.

To screen for new drugs, the researchers tested the ‘pools’ of cells with 1600 different chemicals, using a light-detection technique called luminescence to see if the stem-like cells died in response. As a control, they used immortal breast epithelial cells which hadn’t been genetically manipulated, and each screen was done twice to help ensure the results were valid and not an experimental error. All of this (plating out the cells, adding the chemicals, and measuring the luminescence) were done by robot – although it’s still an awful lot of work!

Kat

Jo Brodie August 14, 2009

Really nice explanation of the cellular goings on.

I take it the ‘high throughput screening’ mentioned in the paper’s title means something like a chip on which umpteen tests can be carried out simultaneously? Might have to investigate this as I don’t know much about it. It was all 96 well plates (http://en.wikipedia.org/wiki/Microtiter_plate) in my day, not that I’ve ever used one though.

Abel Pharmboy August 14, 2009

Note that three other drugs in this paper exhibited selectivity like salinomycin but to a lesser magnitude. Ranking second only to salinomycin was etoposide, a semi-synthetic natural product drug that targets Type II DNA topoisomerases and is already marketed (as Vepesid in the US). My view is that etoposide has not been adequately investigated clinically but I hope that this paper stimulates medics to re-evaluate their protocols.