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New team leaders share their vision for future research (Part 1): cancer evolution

Posted on 27 November, 2013 by lizburtally
Today I've been at our faculty retreat at The Institute of Cancer, London, hearing about some of the cutting edge research showcased by some of our newest faculty members. They join the ICR at a exciting time, as we launch our new Centre for Cancer Imaging and Tumour Profiling Unit, and strengthen our multidisciplinary Cancer Therapeutics Unit. The retreat is an opportunity for everyone to get together and for new faculty members to share their vision for their new teams.

Our Chief Executive, Professor Alan Ashworth, opened the session, stating that the ICR has a big drive to recruit faculty in molecular pathology, imaging, drug development and cell biology – this is to align with our scientific strategy.

This morning we started with talks from the arena of molecular biology, and opened with a fast moving talk by Dr Anguraj Sadanandam. He is aiming to stratify tumours into molecular subtypes -- a goal of precision medicine. Tumours vary widely in terms of genetics and cellular origins, which go to influence how the tumour will behave in terms of severity and response to treatment. Using information such as genetic and metabolic markers, we could subtype cancer patients to identify the most appropriate treatment course, so delivering the greatest benefit to patients. This could be particularly useful in pancreatic ductal adenocarcinoma (PDA) and colorectal cancer. For instance, one PDA subtype is sensitive to erlotinib -- an EGRF targeted therapy -- compared to another subtype, which is sensitive to gemcitabine -- a type of chemotherapy.

I also found Dr Nicola Valeri’s talk particularly interesting, as he is proposing using non-coding regions of the genome as markers to predict a patient’s response to chemotherapy and novel biological agents in cancer. Using microRNAs -- non-coding RNAs controlling cell homeostasis -- we could start to predict a patient’s response treatments in gastrointestinal cancers. It's fascinating that ‘junk DNA’ could open new doors to understanding how tumours respond to treatment.

The late morning session shed some light on the complex concept of cancer evolution. I found this session incredibly interesting and it relates a lot to the heart of our scientific strategy -- personalised medicine. It seems that most of the scientific community are either pessimistic or optimistic towards the outcome of precision medicine. Some people doubt that precision medicine will really work, and ultimately, resistance will occur to all personalised medicines. But some believe that we can forestall resistance, extending the period of response in patients. This can be achieved by predicting clonal expansion -- or evolution -- in tumours and by analysing tumours at the molecular level. If we can detect resistance at the molecular level before it becomes clinically visible, doctors will be able to stay one step ahead of resistance, and can switch the patients therapy before they stop physically responding.

Tumours are tricky. Because they have a huge genetic diversity, this heterogeneity equips them to adapt -- or evolve -- to changing environments, leading to drug resistance. Dr Marco Gerlinger spoke about the hurdles that researchers face when trying to fit personalised treatment for heterogeneous and evolving tumours. Multiple evolutionary clones exist in a single tumour, and researchers are finding it hard to determine which ones influence treatment outcomes -- it’s like trying to hit a moving target. One way to pin the target down is to focus on the common trunk of the evolutionary tree and research has already been done around this. But Dr Gerlinger believes we should be targeting those poor risk clones and focus on the clonal structure -- this is particularly relevant to colorectal cancers. Mutations in KRAS are found on the trunk, but when KRAS negative patients are treated with cetuximab -- a first line treatment for KRAS negative patients with colorectal cancer -- mutations in KRAS can appear overtime. Research shows that KRAS mutations were always present in tumours that became resistant, but were initially only in small numbers and hadn’t clonally expanded. An early switch of treatment would have been beneficial in these cases.

Using cancer evolution as a basis for predicting the behaviour of tumours has massive potential in terms of resistance in precision medicine. The ICR has exciting plans for this area of research, so watch this space for future updates!
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