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Molecular machinery of a dividing cell. Image courtesy of Wikimedia Commons

MPS1 inhibitors block a molecule involved in cell division.

Last year we were extremely excited to launch an innovative fund to bring new cancer drugs to patients.

Today we’re pleased to reveal that the fund has given the green light to its first project, aimed at accelerating the development of a promising group of compounds called MPS1 inhibitors into effective new cancer drugs.

The £50 million fund has been developed to address the sobering reality that the process of turning promising investigational drugs into ‘real life’ treatments for cancer patients is very often unsuccessful. The fund, half of which is provided through our commercial company Cancer Research Technology (CRT), is central to our strategy to make sure that exciting drug discoveries don’t languish at the lab bench, but are given every chance to be transformed into future cancer cures.

Called the CRT Pioneer Fund, it’s being run by independent management firm Sixth Element Capital, who have spent the last few months selecting exciting drug discovery opportunities from around the country.

Read on to find out why work on MPS1 inhibitors by researchers at The Institute of Cancer Research, London, piqued their interest and led to the first grant from the Pioneer Fund.

Checkpoint control

MPS1 inhibitors are a group of chemicals that block the activity of a molecule called monopolar spindle 1 – found inside all our cells. Initially, the early research on MPS1 had little to do with cancer – in the 1990s, scientists found that the molecule played a key role in allowing yeast cells to divide.

But later work showed that human cells also contained MPS1, and that this was part of a larger family of molecules called ‘mitotic checkpoint kinases’. These act like road traffic police, keeping the flow of events during cell division in check, and coordinating the finely tuned movement of cellular machinery as cells divide.

This is extremely relevant to cancer – a disease that happens when this process goes awry, and cells find a way to bypass their internal checkpoints. Indeed, several cancer drugs already in use, such as taxanes, obstruct the cell division apparatus in tumours.

Cop to criminal

Subsequent lab research (handily summarised in this article) showed that MPS1 works at the ‘spindle checkpoint’ in a dividing cell. This checkpoint ensures that chromosomes – which contain our genetic material – attach correctly to the cell scaffold before cells divide. (We wrote about previous research on this process here.)

A key feature of many cancers is that they have an irregular number of chromosomes. Researchers are interested in MPS1 because cancers with abnormal chromosomes often have high levels of MPS1. This seems to allow them to carry on dividing – despite their chromosomal chaos.

In other words, it seems that cancer cells find a way to turn this mild-mannered cop into a cancer-causing criminal.

An obvious big question follows: can scientists develop a ‘chemical handcuff’ to arrest MPS1’s criminal activity and treat cancer? The answer – at least in the lab – is yes.

A few years ago, Professor Paul Workman’s group in the Cancer Research UK Cancer Therapeutics Unit at the Institute of Cancer Research used genetic techniques to dampen down levels of MPS1 in tumour cells grown in the lab and found this killed them. Crucially, healthy cells were unaffected.

Refining a prototype

They’ve since analysed many tens of thousands of chemical compounds, identifying a handful that emulate this cancer-killing effect in the lab. They now have the raw material – the prototype for the chemical handcuff. The next step is to strengthen and refine the design of these ‘handcuffs’ so that they’re suitable to patients as cancer drugs in early-stage clinical trials.

Support from the CRT Pioneer Fund will help the team do this, and we hope accelerate the development of a new drug to treat cancer.

There’s a long road ahead, but we look forward to sharing the results of this research – and news of other Pioneer Fund projects – in the future.

Olly

Comments

Fahmida malik April 24, 2013

Need more checkpoint to save healthy cells.