ASCO 2011 – the challenge and promise of the genomic era

Cancer Research UK’s Senior Science Information Manager, Dr Julie Sharp, reports from this year’s US cancer conference

Dr George Sledge, addressing the ASCO 2011 conference

Around 30,000 cancer doctors and researchers have gathered in Chicago for the annual American Society of Clinical Oncology (ASCO) conference. It’s an opportunity for cancer specialists to hear the very latest results from trials of new treatments, and learn more about hot topics such as personalised medicine or new DNA sequencing technologies.

In his welcome speech, outgoing ASCO president Dr George Sledge discussed the challenges ahead as we enter what he termed an ‘era of genomics’.

In the not-too-distant future, according to Dr Sledge, fast and cheap technologies will be used to map each patient’s genetic make-up, compare it with that of their cancer and highlight all the faults in their DNA that affect how their cancer responds to treatment.

While this information has the power to transform treatment for patients around the world, there are still huge challenges ahead for scientists and doctors. As the costs of analysing – or ‘sequencing’ – DNA plummet, doctors need to find ways to start translating this new genetic knowledge in a way that’s useful and beneficial for patients.

Dr Sledge gave a recent example of how new sequencing technology transformed the care of a difficult-to-diagnose patient with acute promyelocytic leukemia. Scientists at Washington University used whole-genome sequencing to help understand the patient’s cancer and within seven weeks they had enough information to guide the doctor’s decision and change the course of treatment, sparing the patient an unecessary bone-marrow transplant.

‘Stupid’ versus ‘smart’ cancers

Different types of cancer have different numbers and types of DNA faults – and this can vary widely between cancers, with lung cancer and melanoma for example typically having many thousands more faults than other cancer types.

Dr Sledge described cancers as being either ‘stupid’ or ’smart’. The stupid tumours are those that have a single predominant fault (or mutation) that drives the disease and a small total number of different faults in the cancer cells. These cancers, for example many cases of chronic myeloid leukaemia, can be treated with a single drug – glivec – and resistance to treatment is rare.

However, the ‘smart’ tumours have a huge spectrum of faults that fuel the disease. It’s unlikely that doctors will be able to target them with a single drug or treatment, and resistance is more common.

An example of this is non-small cell lung cancer, which can develop resistance to many different drugs. And it now seems that smokers’s cancers are particularly ‘smart’ – lung cancers in smokers usually have many more gene faults in their tumour compared with non-smokers – and so tend to have an even poorer response to treatment.

The Red Queen principle

In Alice in Wonderland, the Red Queen says to Alice – “it takes all the running you can do to stay in the same place”.  Dr Sledge used this quote to highlight the shear effort that will be required to tackle the complexity of these smart tumours. For these cancers there will be no ‘magic bullet ‘– but rather a magic shotgun that is able to fire at multiple targets.

The approaches needed to tackle these smart cancers are varie,d and will include stepping up prevention strategies as well as tackling the biology of the tumour. It will also be important to understand more about the role of the immune system, cancer stem cells and a tumour’s so-called ‘microenvironment’ – the local tissues and molecules that unwittingly help it grow and spread.

And on top of all this, said Dr Sledge, we’ll need a ‘next-generation’ clinical trials system, able to cope with smaller groups of patients who will need to be assessed for a broader range of treatment options, as well as dealing with the incredible amount of data produced by technologies such as next-generation sequencing.

If this sounds more daunting than hopeful – Dr Sledge assured the audience that these challenges can be met by bringing lab science even closer to hospital practice, and by ensuring that cancer doctors are trained to understand this genomic revolution.

Doctors must be able to access all this information quickly and easily from their clinic, and we need to learn how to make sure data from each individual is incorporated into the bigger picture – combining to create a useful ‘whole’.

As Dr Sledge summarised “In the end the principles of treatment will remain the same – being based on the enduring qualities of every cancer doctor: skill and care.”

Julie