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v. Use of human or animal subjects

We have full Ethical Review Committee approval for the use of human patient

samples with appropriate informed consent - reference 10/H0803/126 (South West

London REC3). We have in addition numerous samples including matched

biopsy/autopsy specimens taken with appropriate approval and consent from

collaborating centers worldwide.

vi. Disease Impact and Innovation

There is currently no effective treatment for DIPG. Novel molecularly targeted agents

are destined to fail in the clinic due to the inevitability of resistance, as has been

observed in numerous other cancer types. This is due in part to a wide variation in the

genetic make-up of an individual DIPG sample such that by applying a drug treatment,

we exert a selective pressure on the population of cancer cells that drives the growth

of subpopulations against which the drugs are ineffective. We believe that these

observations mirror those seen in evolutionary biology, and that we need to

understand the extent of the genetic variation present in DIPG samples to make

progress in developing smarter clinical approaches. We plan to apply evolutionary

biology principles to guide new treatment combinations in a way that has not yet hit

the mainstream in any cancer type, and we believe to be a unique undertaking in

childhood brain tumours. The Jones lab has recently been appointed as members of

the newly-launched Centre for Evolution and Cancer at the ICR in London, and will

benefit from a revolutionary critical mass of scientists with expertise in these areas,

with high grade gliomas in general, and DIPG in particular, one of the flagship areas of

research in this initiative.

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