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Where are we going with patient care, genomics and targeted therapies?

Posted on 04 November, 2014 by Liz Burtally

Yesterday Professor Richard Marais opened the 10th National Cancer Research Institute (NCRI) conference celebratory talks by setting the scene for the session’s big-hitting speakers. He told a packed lecture theatre, “At this 10th year it's important for us to see where we have come from and where we are going in the fields of patient care, genetic basis of drug discovery and genomics."

The first of the three celebratory talks was from Professor Sir Mike Richards, Chief Inspector of Hospitals for the Department of Health. He opened the session with an overview of the last 30 years in cancer services.

It seems we have come a long way since the 1980s, which Professor Richards referred to as ‘the dark ages’, where there was little open discussion about cancer. Even though we have progressed brilliantly in the last 30 years, with many new initiatives in research and patient care launched, we still have a lot of work to do.

Dr William Sellers, director of cancer drug discovery at the Novartis Institutes for BioMedical Research, discussed the future of targeted therapies – stressing that we need to look at the oncogenes that are traditionally hard to target (such as transcription factors), target tumour suppressor pathways (with a particular focus on synthetic lethality) and deal with therapeutic resistance by thinking about combination and sequential therapies.

It was the middle talk of the session that especially grabbed me though, with Professor Sir Mike Stratton giving a virtuoso overview of the field of genomics. Fifty years ago things were much more basic than today, focusing on cytogenetics and copy number changes. Moving into the 1980s we were performing copy number analysis and the harvest for cancer genes began, resulting in 2,000 cancer genomes sequenced. Now, we have sequenced nearly 20,000 cancer genomes.

So what have we been able to do with all this information? We have identified large numbers of drug targets - 600-700 cancer genes have been identified and many are potentially druggable.

But we have discovered that there are few common mutations, and the majority of mutations are found in less than 10% of patients. We’re likely to be looking at different drug targets, in other words, in the many different genetic sub-types of cancer.

Genomics has given us a fantastic insight into cancer evolution – giving clues, for instance, about how metastasis starts. Researchers are beginning to be able to use circulating tumour DNA for early detection of cancer, and to predict outcome and response to therapies.

And where can we expect genomics to take us next? Professor Stratton, Director of the Wellcome Trust Sanger Institute, suggested that in the next five years, we would see the next round of genome sequencing. He predicted we would uncover many more new mutations that occur only infrequently in cancer – the ‘long tail’ of cancer genomics – and would ultimately need to decide how long to keep on going in characterising cancer.

Professor Stratton finished by stressing that the costs of sequencing are getting lower and lower – he estimated that one mutation costs around £60 to sequence, compared with £1,200 for the whole genome.  Gradually, over time we can expect the differential between sequencing a gene and sequencing a whole genome to get smaller and smaller - adding fuel to the genomics fire.


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