Hopes that doctors will one day offer personalised treatments for cancer patients have received a boost from a landmark study into the ability of a huge range of drugs to destroy different forms of the disease.

In the largest project of its kind, researchers tested how well 265 old and new drugs worked on cancer cells that harboured most of the important DNA mutations that drive various types of tumours.



In hundreds of cases, the scientists found that drugs which were either already in use or under development in laboratories destroyed cells when they carried key DNA mutations found in many different kinds of cancer.



The findings show how existing drugs could potentially be repurposed to treat new groups of patients, or be more effective in people whose tumours have specific genetic abnormalities. The work will also help researchers design drugs that can target cancers based on their DNA signatures.



“We want to understand which patients will respond to which cancer drug, and find the mutations that will allow us to select patients that will be most likely benefit,” said Matthew Garnett, a cancer biologist who led the research at the Sanger Institute near Cambridge.



Cancer tumour genetics reveal possible treatment revolution Read more

The researchers began by gathering details on the genetic mutations known to cause cancer in 11,000 tissue samples that represented 29 different tumour types. Armed with the catalogue of mutations, they went on to identify 1,001 batches of cancer cells used in lab work that between them carried nearly all of the key mutations.



For the next step, the team treated the cells with 265 cancer drugs and noted which mutations most successfully predicted whether a drug killed the cancer cells or left them unscathed. In the future, the findings could inform genetic tests that allow doctors to personalise the treatments patients receive.



“There are so many genetic alterations in cancers, and there are so many drugs, that we can’t possibly test them all on patients. It’s not feasible, and it’s not ethically appropriate,” Garnett. “Cancer is so diverse that we really need to look across large sets of these cells to understand which patients will respond to a drug and which won’t.”



The study, published in the journal Cell, confirms much that is already known about the mutations that make cancer cells susceptible to drugs. But it found plenty of completely new links between abnormal DNA and drug effects too, which will now be pored over in the hope of developing more powerful cancer treatments.



The findings already point to a way in which one cancer drug might be used more effectively. Mitomycin C is used to treat bladder cancer, but according to the study the drug is particularly effective against a subset of bladder tumours that carry a certain mutation. “With these kinds of data, we may be able to explain why some patients fare better than others,” Garnett said.



But more work is needed before the results can begin to help patients. The discoveries made with the cancer cells must be checked in animals before human clinical trials. “This will steer decisions about drug development immediately, and it’s possible that in two to five years, it will start to inform clinical practice,” Garnett added.



The Sanger team is now creating a web portal to share their data. Allowing cancer researchers around the world to see which batches of cancer cells most closely mirror the patient tumours they hope to treat.