Source: New Scientist – Michael Slezak.
Pancreatic cancer’s deadliest trick could be its undoing. Despite each person’s tumours having very different genetic mutations, they all cause the same metabolic changes that help it grow. What’s more, drugs already exist that can block the process.
Pancreatic cancer is the most lethal of all common cancers – 95 per cent of people die within five years of diagnosis. One reason it is so deadly is that no two cases are genetically the same. That means the tumour is more likely to evolve resistance to drugs, and that genomic studies aiming to find common mutations that could be targeted by treatment have fallen flat.
So Darren Saunders and colleagues at the Garvan Institute of Medical Research in Sydney, Australia, tried a different approach. As well as looking for variations in the genome of different people’s tumours, they also looked at the biological processes at work in the cells.
To do this, they switched from using dead tumour cell samples to patient-derived tumour cell lines, in which fresh samples of a person’s tumour are grafted onto mice and grown to the required volumes. Growing them in animals makes for more lifelike tumours, and can produce large quantities of tissue for study.
This bank of living tumour cells allowed the team to study not only the genetics of the cells, but also how genetic mutations in the mitochondria – which drive energy production in the cell – caused changes in the cell’s metabolism.
To analyse the tumour cells’ metabolism, they used a technique called “metabolomics“. This involves crushing live tumour cells and measuring the metabolites they contain using a mass spectrometer.
“You can think of it like lines on a train map,” says Saunders. “Metabolomics allows us to map those pathways and see which ones are switched on and switched off [in a cell].”
Putting together their analyses of the mitochondrial DNA in each tumour cell line and the metabolic pathways at work, the team were able to deduce how each cell line’s genetics directly affected its ability to multiply.
They found that pancreatic cancer cells consume not only glucose, as normal cells do, but also glutamine. This leads to the production of fatty acids – the building blocks of new cells – thereby allowing the tumours to proliferate wildly. “Instead of using fuel for energy, they switch to using fuel to build new cells,” Saunders says. The team presented its results at the Lorne Cancer Conference in Australia last month…Read the full article