New computer tool to boost development of cancer drugs

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Cancer patients could benefit from more effective treatments thanks to a new computer tool which predicts how tumours will respond to drugs.

Scientists say the sophisticated software can be used to overcome mutations in cancer cells which lead to drug resistance.

The new program could help with the discovery of new cancer drugs by predicting how tumours will become resistant to treatment long before it would first become apparent in clinical trials.

Dr Teresa Kaserer, Higher Scientific Officer at the Institute of Cancer Research (ICR), London, said: “Our new approach can predict which mutations are likely to arise in response to drug treatment in different types of tumours.

“This will be hugely beneficial in designing new cancer drugs.

“Instead of reacting to what we see in the clinic – when it’s too late as patients have stopped responding to treatment – we can use our computational method to predict during the drug design stage how resistance will arise.

“It means we can begin designing second-generation treatments much earlier, as well as developing tests to select patients for treatment and monitor them while on the drug.

“This could be great news for patients, who could be switched to a second generation drug as soon as a resistance mutation appears.”

The prediction tool, which has been featured in the journal Cell Chemical Biology, starts by analysing all the possible mutations that could occur against cancer drugs, usually between 350 and 1,200. The researchers then use prediction software to find nine or 10 mutations most likely to cause drug resistance before laboratory tests are carried out.

Professor Julian Blagg, Deputy Director of the Cancer Research UK Cancer Therapeutics Unit at ICR, and study co-author said: “In recent years, targeted cancer therapies have brought significant benefits to patients, but the eventual emergence of drug resistance remains a major challenge.

“Predicting how a cancer drug target may mutate to kick out the therapeutic agents whilst maintaining its normal function can help us stay one step ahead of tumour evolution by creating new treatments that block a cancer’s escape routes.

“Our study has explored one of the ways tumours can become resistant to cancer drugs, but there are other escape routes cancer cells can take to avoid destruction.

“Our approach is an important first step, and we, along with other colleagues at the ICR, are looking to develop similar tools to identify, right at the start of cancer drug discovery, the alternative roads to drug resistance.”

Researchers said that for the cancer drug imatinib, the program accurately predicted a common mutation that causes resistance in some patients.

The tool also correctly predicted that the second-generation version of the drug would not be affected by the mutation.