Researchers have today published a new “encyclopaedia” detailing how hundreds of different cancer cells respond to anti-cancer agents, BBC News has reported.
The research is part of a high-profile project to unlock how genetics controls the way cancerous cells respond to chemotherapy and drugs in the lab. It could potentially lead to personalised treatments. For example, if a patient were to have their tumour tested, doctors could potentially choose the best drug based on the tumour’s specific characteristics.
The initial results that will form part of the encyclopaedia have been published in two large studies. These provide details on hundreds of different laboratory-grown cancer cell lines. Cell lines are isolated cells that mimic the characteristics and genetic diversity of human cancer cells. Each of these cell lines was exposed to more than 100 drugs, and data were collected on the effectiveness of thousands of different cell and drug combinations, at least in a laboratory setting.
Why build a cancer encyclopaedia?
Drug development trials and clinical trials have shown that tumours, even from a single type of cancer, can respond to cancer drugs in different ways. A drug can prove highly effective in one patient but produce little effect in another, even with a seemingly similar cancer. Also, drug companies have long struggled to work out which patients are most likely to benefit from a drug in advance of clinical trials. As cancer is caused by faulty genes (segments of DNA), leading to uncontrolled cell growth, scientists have long sought to predict which drugs will be effective based on the genetic characteristics of the cancer cells.
Cancer treatments are already increasingly being tailored to the particular genetic characteristics of a tumour, but this shift in treatment practice is in its early stages. This type of approach has become known as “personalised medicine”. In the field of cancer this could lead to treatment being tailored according to the specific genetic characteristics of the cancer cells of the person being treated. Currently, many cancer drugs only work in a small proportion of patients who are given them. Gaining extra knowledge in advance about who is most likely to benefit is a desirable research aim.
The authors behind the cancer encyclopaedia, which is available to the whole cancer research community, hope their database will be an important resource for the scientific community and ultimately lead to better treatment for patients with cancer.
Having a cancer encyclopaedia may aid drug development by improving our understanding of how drug effectiveness is linked to cancer genetics. It provides information to researchers, drug companies and health professionals about which types of drugs are most likely to work on different types of cancers, and how this is linked to the genetic characteristics of the tumour cells.
How is the research being performed?
Laboratory-grown cancer cells are frequently used by researchers studying cancer and developing new drugs. However, results from laboratory cells do not always translate into clinically useful results as the cells grown in the lab are not surrounded by other cells in the body. Furthermore, drugs that are added in the laboratory do not have to circulate in the body before reaching the cells, so may have different effects.
Despite these differences, laboratory tumour cells are very useful in cancer research as they allow researchers to test large numbers of drugs in large numbers of cells relatively quickly. In some cases this can be automated using robotic technology, speeding up the process and allowing many combinations of drugs and cancer cells to be tested rapidly. The sharing of the results through a single, centralised source also means that there is likely to be a reduction in overlapping research, so that time, money and valuable resources are not needlessly committed to researching the same premises repeatedly.
The two new studies published today provide an overview of how the research constituting the encyclopaedia could work and the type of results it can provide. In the studies, researchers analysed and documented the detailed genetic features of hundreds of laboratory-grown cancer cell lines, mimicking the many different types of human cancers. The researchers then cross-referenced these genetic characteristics with the way the cells responded to approved drugs, as well as drugs in development. Now that the results of these two studies have merged they provide the most complete picture yet of how genetic differences shape a cancer’s response to drugs.
The first of these studies assessed the genetic information of 947 cancer cell lines and exposed 479 of these cell lines to 24 different anti-cancer drugs to test how sensitive they were to the drugs. The second study profiled the genetics of 639 cancer cell lines and how they responded to 130 drugs. Together the studies provide detailed information on thousands of combinations of drugs and cancer cells, as well as the genetic factors governing how these cells responded.
The collaborative research was funded by the Wellcome Trust. Any financial links between the researchers and pharmaceutical companies are declared in the reports.
What has it found so far?
Both research groups have already been able to use their “cancer encyclopaedia” to highlight potential new avenues for treating a type of cancer called Ewing’s sarcoma, a rare bone cancer that affects mainly children and young adults. One of the teams, for instance, found that Ewing’s cancer cells were sensitive to a certain type of drug called PARP inhibitors. Nature News reported that one of the PARP inhibitors is already being tested as a treatment for other cancers in clinical trials, and that the encyclopaedia findings may speed up the transition to testing this drug against Ewing’s sarcoma in the future.
How could the results be used?
The research authors hope the results of the encyclopaedia can eventually be used to help predict which types of cancer cell will be sensitive to anti-cancer drugs so that treatment of people with cancer can be tailored to the individual. This would work by assessing the genetic characteristics of extracted cancer cells and matching them against the best available drugs according to the encyclopaedia’s results.
The encyclopaedia can do this by helping to guide current cancer research by highlighting previously unknown links between the genetics of a cancer and its reaction to new or existing drugs. The discovery that PARP inhibitors may be useful in the treatment of Ewing’s sarcoma is a good example of this in action.
It is hoped that this type of research could lead to better methods of predicting which cancer drugs will be most effective for treating cancer patients, based on the genetics of their particular cancer. Crucially, this could help predict the best drug for the job before the drug is given, potentially reducing the number of drugs given inappropriately or minimising unnecessary side effects caused by giving a range of drugs that are unlikely to work.
Developing personalised, targeted cancer treatments around an individual’s specific tumour, rather than simply trying the best option for the broad type of cancer they have, has long been a goal of cancer treatment. This research paves the way for a new phase of research aiming to unlock the way genetics controls the behaviour of cancer cells, and eventually this may lead to great improvements in the way people with cancer are treated in the future.
Cancer: 'Book of knowledge' published. BBC News. March 28 2012
Garnett MJ, Edelman EJ, Heidorn SJ, et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Published online 28 March 2012
Jordi Barretina J, Caponigro G, Stransky N, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Published online 28 March 2012
Nature News: Cancer screen yields drug clues. Published March 28 2012
Wellcome Trust Sanger Institute: The path to personalised cancer treatment. March 28 2012