29-Mar-2012

Drug sensitivity encyclopedia will aid cancer research

A Cancer Cell Line Encyclopedia (CCLE) produced by scientists from Novartis and the Broad Institute, Harvard Medical School could accelerate the development of personalised cancer treatments.

The CCLE, available online as a public resource, catalogues the genetic and molecular profiles of nearly 1,000 human cancer cell lines used in drug research and development.

Another team of scientists from Massachusetts General Hospital in the US and the Wellcome Sanger Institute in Hinxton, UK have also screened several hundred diverse cancer cell lines with 130 drugs under clinical and preclinical investigation to help identify new biomarkers of drug response.

According to William Sellers, global head of oncology at the Novartis Institutes for Biomedical Research (NIBR), the CCLE will ‘provide scientists with the ability to build predictive models of what types of patients will respond to a particular class of drugs’.

The cell lines were acquired from commercial vendors in the US, Europe, Japan and Korea and represent a diverse picture of cancer as they include many subtypes of both common and rare forms of cancer.

The Broad Institute reports on the CCLE in a paper in the journal Nature. Lead authors and NIBR researchers Jordi Barretina and Giordano Caponigro, say each cell line was genetically characterised through a series of high-throughput analyses at the Broad Institute, including global RNA expression patterns, changes in DNA copy number, as well as DNA sequence variations in about 1,600 genes associated with cancer, and pharmacologic profiling for several drugs in about half of the cell lines.

Algorithms were developed to predict drug responses based on the genetic and molecular makeup of cancer cells.

Pairing this information with ways to genotype patient tumour samples represents the next step in the effort to enable the personalisation of cancer treatment, the researchers say.

The Massachusetts General Hospital and Wellcome Trust Sanger Institute team, which also published their results in Nature, discovered from their initial data that cells from Ewing’s sarcoma, a childhood bone cancer, respond to a drug that is currently used in the treatment of breast and ovarian cancers. The lowered toxicity of this treatment may mean it is a safer alternative therapy for children and young adults with this aggressive cancer.

Dr Ultan McDermott, senior author from the Sanger Institute, said: ‘Advances in next-generation sequencing technologies are already being translated into the large-scale detection of cancer gene mutations in the clinic.

‘There is a compelling need to identify, in a systematic fashion, whether observed mutations affect the likelihood of a patient’s response to a given drug treatment. We have therefore developed a unique online open-access resource for the research and medical community that can be used to optimise the clinical application of cancer drugs as well as the design of clinical trials of investigational compounds being developed as treatments.’

Professor Charles Swanton, a Cancer Research UK expert, said both databases would be ‘an invaluable resource’ and provide ‘extremely useful intelligence to cancer researchers and those working in cancer drug development’.

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