23rd December 2008

A new search for cancer treatments

Genome study will drive forward targeted approach to cancer

HeLa Cells

Human HeLa cells in culture, showing the nuclei in red and the tubulin component of the cytoskeleton in green. The blue staining is a mitotic checkpoint protein that remains in the cytoplasm until pro-metaphase when it is involved in regulating cell division. HeLa cells are derived from a human cervical cancer and can be propogated indefinitely in culture. [Matthew Daniels, Wellcome Images]

The quest for personalized cancer treatments is given a boost today by the announcement of a $13M (£8.5M) UK-US alliance to find the best treatments for cancers. The scientists will use their skills in high-throughput research to test the sensitivity of 1,000 cancer cell samples to hundreds of known and novel molecular anti-cancer treatments and correlate these responses to the genes known to be driving the cancers.

Their results will give a catalogue of the most promising treatments or combinations of treatments for each of the cancer types based on the specific genetic alterations in these cancers. This information will then be used to empower more informative clinical trials thus aiding the introduction of more targeted agents into the clinic.

The project is co-led by Professor Mike Stratton FRS and Dr Andy Futreal of the Sanger Institute, near Cambridge, UK and Professors Jeff Settleman, PhD and Daniel Haber, MD, PhD of Massachusetts General Hospital Cancer Center Boston, USA. Dr Haber is also a Howard Hughes Medical Investigator.

"Cancer remains a disease that affects directly one in three of the world's population," explains Professor Mike Stratton, co-Head of the Cancer Genome Project at the Sanger Institute. "But we have new tools that we can bring to bear. Our emerging understanding of cancer mutations allied to our abilities to carry out large-scale research means we can develop screening techniques to find the most effective treatments for a whole variety of cancers."

"This exciting project builds on the complementary skills of the two institutions and demonstrates how knowledge of the abnormal human genome in cancer cells can now be used on a large scale to explore and predict responses to novel and conventional anti-cancer drugs," explains Professor Stratton.

The five-year project, funded by a Strategic Award from the Wellcome Trust, is to be conducted by the Wellcome Trust Sanger Institute and Massachusetts General Hospital Cancer Center. The teams will make extensive use of the genetic information being produced by the Sanger Institute Cancer Genome Project to draw the important correlations between anti-cancer agent response and the catalogue of genetic abnormalities known in each sample.

The experimental work will be split equally between the two collaborating institutions but will harness the previous experience in experimental exposure of cells to molecular treatments at Massachusetts General Hospital Cancer Center and the skills in large scale genomics, sequencing and informatics at the Sanger Institute.

" Our emerging understanding of cancer mutations allied to our abilities to carry out large-scale research means we can develop screening techniques to find the most effective treatments for a whole variety of cancers "

Prof Mike Stratton

"Targeted cancer drugs have emerged in recent years as an important new class of anti-cancer agents, and can yield dramatic clinical responses in some cancers. We hope to improve our ability to direct these drugs to the patients that are most likely to benefit," explains Professor Settleman, Scientific Director of Massachusetts General Hospital Cancer Center. "Previous pre-clinical experimental studies of such agents have typically examined their activity in a small number of cancer-derived cell lines, providing little opportunity to determine where they will be truly effective in the clinic. The collaborative study will make use of a very large collection of cancer cell lines of known genetic composition to identify genomic features that underlie drug sensitivity. Such information will be of tremendous value in informing the design of clinical trials for new candidate anti-cancer drugs and for making treatment decisions between available drugs."

'Cancer' encompasses a group of more than 100 different diseases caused by a bewildering array of mutations in different genes of different types. The outcome of this ambitious drug profiling effort will yield a description of which genetic alterations found in a broad spectrum of tumours predict response to which of approximately 400 anti-cancer treatments being investigated. This will inform targeted clinical trials where patients will be given different treatments depending on the genotype of the mutated cancer cells.

"The pace of research in human genetics is breathtaking. The Human Genome Project has enabled the identification of the mutations that cause certain cancers," says Dr. Mark Walport, Director of the Wellcome Trust. "Following the work of Professor Mike Stratton at the Sanger Institute and others, an International Cancer Genome Project is underway that will identify the mutations that cause the 50 commonest types of cancer around the world. The challenge is to use new genetic knowledge about the causes of cancer to find new treatments and this project aims to do just that."

"This significant and strategic project is aimed squarely at providing the first step towards tailored cancer therapy," adds Dr. Ted Bianco, Director of Technology Transfer at the Wellcome Trust. "The ultimate target is to give doctors the tools to identify the best therapy for each individual patient according to the genetic characteristics of their particular tumour, rather than basing these decisions solely on where the tumour has developed. We're especially delighted to be working with the team at Massachusetts General Hospital Cancer Center on this ambitious programme of research."

Cell lines are grown artificially - in culture - and are originally derived from naturally occurring human cancer tumours. This study will use publicly available cell lines, allowing other investigators to replicate and develop further the results, to ascertain the sensitivity of different cell lines to different treatments and to discover which genetic alterations affect this sensitivity.

"This transatlantic collaboration brings together two outstanding research teams focused on cancer genetics and therapeutics," says Dr Daniel Haber, Director of the Cancer Center at Massachusetts General Hospital. "The future of cancer treatments is precisely the ability to match specifically targeted drugs to the personal genetic lesions in each cancer, and this joint research effort is likely to generate important new information that will drive clinical research in the near future."

Clinical responses to anti-cancer therapeutics are often restricted to a subset of cases and accumulating evidence indicates that response often correlates with a specific tumour genotype. It is hoped that response rates could be substantially improved by directing treatment towards genetically defined subsets of patients most likely to benefit.

The findings of the programme will be validated in clinical specimens and will subsequently inform the design of clinical studies to examine patient response against the genetic information.

Notes to Editors

Massachusetts General Hospital Cancer Center

An integral part of one of the world's most distinguished medical centers, the Massachusetts General Hospital Cancer Center is chosen by more cancer patients than any other hospital in New England. Its commitment to eradicating cancer is fueled by scientific investigation conducted as part of the largest hospital-based research program in the United States.

Known for providing individualized, compassionate care to both adults and children, the Cancer Center comprises 18 fully integrated, multidisciplinary clinical programs and a vast network of support and educational services.

It is a founding member of the DF/HCC, a Harvard Medical School consortium designated by the National Cancer Institute as a comprehensive cancer center. This prestigious seven-member center forms the largest cancer research collaboration in the country. Also, Massachusetts General Hospital Cancer Center and Dana-Farber/Brigham and Women's Cancer Center collaborate on joint clinical trials, education, training programs and quality of care improvements.

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The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.

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The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.

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