Forensic cancer treatment: Personalised drugs therapy becoming a reality with hopes for improvement in survival rates

 

A decade ago it took tens of millions of pounds and many years to sequence the compete genome of one individual. Now it takes a few hundred pounds and a couple of days to decode the entire DNA of a cancer cell.

The rapid pace of change in DNA sequencing is leading to a transformation in the diagnosis and treatment of cancer. In the coming decade every cancer patient will receive a genetic profile of their disease, scientists predict.

An era of personalised medicine where patients receive tailor-made treatments based on their DNA rather than their just their symptoms could end the one-drug-treats-all approach to cancer treatment, which has failed many patients in the past, they said.

The revolution will also mean that the classic method of testing new drugs and treatments based on large-scale clinical trials with thousands of patients will be replaced by a more targeted approach focussed on a smaller number of individuals with known genetic profiles.

Rapid DNA sequencing will usher in a new era of discovery where cancer drugs will be tailor-made for those patients based on the type of DNA mutations carried within their tumours, scientists said.

“In part it might signal a significant shift in the way medicine is performed for cancer in the 21st Century,” said Professor Alan Ashworth chief executive of the Institute of Cancer Research in London which has just opened a new tumour profiling unit to rapidly sequence the DNA of cancer samples.

“None of this is science fiction. It’s happening in a number of places around the world but we feel it will be absolutely routine within the next five to ten years for every cancer patient,” Professor Ashworth said.

It could mean that drugs designed for one type of cancer will be used in the treatment of a quite different cancer as scientists uncover common biochemical pathways that link one disease to another, Professor Ashworth said.

“It opens up the possibility of using drugs in a context in which they were not originally developed,” Professor Ashworth said. It could also change the whole approach to drug development and clinical trials.

Instead of having to rely on large “phase-3” trials involving several thousand patients followed for many years to determine small, statistically significant improvements, doctors could go straight to a new therapy based on their discretion, knowing that a drug can target a particular DNA abnormality, he said.

“In the past, drugs have been developed with large, phase-3 clinical trials involving thousands of patients and working out what is best for the average patient. What we are saying now is to turn this on its head – to look at what is best for the individual patient,” he said.

“It may be that in certain rare cancer types, a drug might be considered effective, even though there may well never be clinical trial evidence to prove it,” he added.

Classical clinical trials have essentially failed certain types of cancer patients, such people with tumours of the pancreas and lung, where the improvements in treatment have been minimal, Professor Ashworth said.

Similarly, some existing cancer therapies are known to be ineffective in a large number of patients who routinely receive the treatments – but DNA profiling could help to end this harmful waste, he said.

“In chemotherapy for women with breast cancer, for instance, only about one in ten receives any benefit from the treatment. So that means you are massively over-treating the population – nine out of ten receive essentially no benefit,” Professor Ashworth said.

“We want drugs that work on more patients and for longer, so let’s design the trials to deliver that and design the trials for success rather than failure,” he said.

“Basically the way we’ve been developing drugs for cancer is now failing big time. There’s not that many new drugs approved each year and certainly the idea of developing old-fashioned chemotherapies is going out of the window,” he added.

Drug resistance is one of the biggest problems to emerge from the use of new drugs targeted at certain DNA profiles. Resistance is a Darwinian process – cancer cells continue to mutate and those that are resistant survive the therapy and quickly spread around the body.

“The biggest obstacle to personalised medicine is really resistance, and understanding what causes resistance. But this is not black magic it is something that can be defined, quantified and understood, and then exploited,” Professor Ashworth said.

“Some people have taken this as a sign that personalised medicine isn’t working but the answer to that is that it’s still early days. These drugs have just been developed, we’re working out how to use them and we’re starting to understand what the resistance mechanisms are. It’s going to be much more complicated than giving a single drug and getting a cure,” he said.

Personalised medicine could actually save the NHS money in the long term if it prevents patients from developing metastatic cancers that have spread from the original site of the tumour.

“It costs about £100,000 to treat a woman with metastatic breast cancer. We can do DNA profiles for a few hundred pounds. The clinical management costs will far outweigh the diagnostic costs,” Professor Ashworth said.

“I think with early-stage disease, we will be curing more people. With advanced disease, we are talking about keeping people alive, and more importantly well, for longer” he said.

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