17 December 2012

Appeared in BioNews 686

Genetic mutations are not the only contributing factor in the growth of cancerous tumours, say scientists. Research showed tumour cells that were genetically indistinguishable had varying capacities for cell division and resistance to chemotherapy treatment.

'I thought we'd be able to look at the genetics that let some cells propagate, or not be susceptible to chemotherapy, but lo and behold there was no genetic difference', said Professor John Dick of the University of Toronto, Canada, who led the study. 'That goes against a main dogma of the cancer enterprise: that if a tumour comes back after treatment it's because some cells acquired mutations that made them resistant'.

Cells from ten human colorectal cancers were injected into mice, resulting in tumours. The cells were marked with a molecular tag, allowing the researchers to track them, as they were transplanted from one mouse to another. The behaviour of the cells was charted from mouse to mouse, for up to five transplantations.

Some cells were responsible for tumours in every mouse, while others were more variable, only appearing in tumours in the first mouse or laying dormant initially and becoming active in tumours in subsequent mice. The different behaviours of these cells were not reflected in their genomes, which showed 'remarkable genetic stability', commented Professor Dick to The Scientist.

Researchers then investigated the behaviour of these tumour cells in response to the chemotherapy drug oxaliplatin. Cells that were persistently active in tumours from mouse to mouse were killed off. However cells considered dormant, survived the treatment with oxaliplatin and became active.

'The conclusion that we came to was that there must be non-genetic mechanisms that are governing drug resistance', said Professor Dick.

Professor Steven Libutti from the Montefiore Einstein Center for Cancer Care, who was not involved in the study, told Reuters: 'In my mind, the findings are not unexpected. Other things besides genes matter: the environment in which a tumor is growing, for instance, plays an important role in whether therapy will be effective'.

The study has provoked debate around 'personalised medicine' for treating cancer: 'It's not as simple as just sequencing mutations to tailor therapies to each tumor', remarked Professor Libutti.

'What our paper is saying is that on top of [targeting] the genetic properties of these cells you have to target the biological properties to be more effective', said Professor Dick to the Toronto Star. 'Everything doesn't just rest on genetics'.

The study was published in the journal Science.