Targeting leukaemia at the roots

A white blood cell, courtesy of the LRI Electron Microscopy Unit

We recently blogged about the latest cancer stem cell breakthrough that hit the headlines – announcing that US scientists had discovered a chemical that could kill breast cancer stem cells in the lab.

There’s a good reason why cancer stem cells are causing such a stir – if scientists can unlock their secrets, it could lead to powerful new ways to hit cancer at its very roots. And that translates into a very big prize – more effective cancer treatments and improved survival for patients.

So we’re really excited to tell you about another new piece of research that Cancer Research UK is funding in this cutting-edge field – led by Professor Tessa Holyoake at the University of Glasgow.

Her team is looking at ways to better target leukaemia stem cells, hopefully improving treatment for people with a certain form of the disease called chronic myeloid leukaemia, or CML.

Kat’s already blogged in depth about the science behind cancer stem cells, which some scientists think are responsible for several different types of cancer, including forms of breast, prostate and bowel cancer.

Out of all the millions of cells that make up a cancer there is a very rare kind – called cancer stem cells – that fuel the growth of the disease. Current chemotherapy and radiotherapy treatments don’t hit the stem cells, explaining why some people’s cancers can come back – or relapse – over time. Cancer stem cells are particularly relevant to leukaemia, the type of cancer where they were first discovered.

Leukaemia and cancer stem cells

Leukaemia is a cancer of the white blood cells, which circulate in our blood and protect our body from infections. They’re short-lived, so our supply is constantly replenished by stem cells in our bone marrow, churning out millions of new white blood cells every day.

In leukaemia, this process gets out of control and the cells divide too quickly, releasing many immature cancerous white blood cells into the bloodstream. And research has shown that at the heart of the cancer is a small population of rogue stem cells.

The good news is that a drug called imatinib (Glivec) – one of the ‘new generation’ of cancer drugs – has transformed the outlook for the vast majority of people with CML.

It is designed to specifically ‘home in’ on a particular faulty molecule involved in driving cell growth in CML cells.

However, although CML can be controlled for many years with imatinib, it is not necessarily cured. This is because, although it can kill the ‘bulk’ leukaemia cells, imatinib doesn’t kill the cancerous blood stem cells at the root of the disease. Instead, it stops them from growing, effectively sending them to ‘sleep’.

In most cases a patient’s disease is effectively controlled – but only if they receive continuous treatment with imatinib, often for many years. But unfortunately, this also means that the CML stem cells still survive and over time, they can develop resistance to the drug.

So eventually the disease can come back or ‘relapse’- in a form that is resistant to imatinib.

Tackling imatinib resistance

Back in 1999, Professor Holyoake was the first to identify the existence of CML stem cells that are resistant to imatinib. And her new research programme is all about understanding why. By finding out what sets the CML stem cells apart from the healthy stem cells, and the rest of the ‘bulk’ cancer cells, she aims to develop new ways to target and kill them.

Her team’s first step is to identify genes that are key to CML stem cells surviving treatment. They are using a number of different approaches – including sophisticated experiments to compare the activity of genes in healthy blood stem cells with CML stem cells. And they are also growing human CML stem cells in the lab and treating them with imatinib – to monitor changes in gene activity as the cells develop resistance to the drug.

In their preliminary lab studies, the scientists have already identified key differences in the CML stem cells that may be important for their survival. They’re now following these up to see whether they could be exploited by developing drugs that block their activity.

Future hopes

At the moment, this is fundamental basic lab research, but in the future it could lead to new strategies for developing treatments that specifically target CML stem cells.

The hope is that any new ‘cancer stem cell-busting’ treatment, given in combination with drugs like imatinib, would totally eliminate all CML cells – both stem cells and ‘bulk’ cells –  in the early ‘chronic’ phase of the disease. Importantly, as well as improving long-term survival, this would also mean that patients would not need to have drugs for very long periods of time  – which would reduce both side effects and cost of treatment.

Cancer Research UK is already funding a number of researchers studying cancer stem cells in this cutting-edge field. So we’re really excited to add to this list with Professor Holyoake’s new research programme.

Although it’s still early days, we hope that studying cancer stem cells will lead to more effective ways to treat many different types of cancer, improving survival and quality of life for many more patients in the future.

Alison Ross, Senior Science Information Officer