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The personalisation of cancer treatments is leading to better outcomes for patients

Personalised cancer treatment, long talked of, is thus now becoming real. By detecting problems earlier and getting therapies right first time, it will save lives which might otherwise be lost. Better molecular understanding of the underlying processes of cancer, meanwhile, will extend the range of lives that medicine can aspire to save. There is still a long way to go. But gradually and inexorably the appeals court of oncology is tearing up cancer’s death warrants.

 

The past five years have seen a torrent of innovation in the treatment of cancer. More than 70 new drugs have come to market, and for some of these describing their consequences as revolutionary is not hyperbole—at least for those patients lucky enough to respond to them. A diagnosis of advanced melanoma, for example, was once tantamount to a death warrant. Median life expectancy after such news was six to nine months. But recently developed “immuno-oncology” drugs, which exploit a patient’s immune system to fight his tumours, are so effective that, in around a fifth of cases, there is real debate among experts as to whether the patient has actually been cured.

“Cure” is not a word much used by oncologists. The best they normally talk of is “remission”. This sort of upbeat news is reinvigorating the study of cancer. And it is not the only thing to do so. As they are showing at this year’s meeting of the American Society of Clinical Oncology (ASCO), which is taking place in Chicago at the moment, the subject’s practitioners have a spring in their step. Not only do they have new drugs to deploy, they are also developing better ways of using existing ones. They are getting better at diagnosis, too, finding methods to study the weak spots of cancers in parts of the body conventional biopsies cannot reach, and also to pin down tumours that were previously unlocatable. The upshot is that they are beginning to be able to tailor treatments to the needs of individual patients, an approach known as personalised medicine.

 

Picking winners

These days cancer is seen less as a disease of specific organs, and more as one of molecular mechanisms caused by the mutation of specific genes. The implication of this change of viewpoint is that the best treatment for, say, colorectal cancer may turn out to be something already approved for use against tumours in an entirely different part of the body, such as the breast . One study being presented at ASCO has found that 29 of 129 patients responded to drugs that had been approved for use on cancers found in different parts of the body. Therapies for breast and gastric tumours involving a gene called HER2 were particularly useful in this regard. These HER2 drugs act on a growth-promoting protein that is overproduced in HER2-positive cancers. Seven of 20 patients with colorectal cancer, three of eight with bladder cancer and three of six with bile-duct cancer responded well to these drugs. 

Another study, a “meta-analysis” of almost 350 early-stage drug trials which gathered the results of these individually small experiments together in a statistically meaningful way, tried to work out how much benefit there was in trying to match the molecular characteristics of the tumour of a patient with his treatment. Such matching proved worthwhile. Using it caused tumours to shrink by an average of 31%. Established treatments without such matching resulted in an average shrinkage of only 5%.

ASCO itself sees so much value in this approach that despite its being a professional body for doctors rather than a research organisation in its own right it has decided to run a clinical trial (its first ever) to look at personalised medicine’s potential. TAPUR, as this trial is called, will offer patients a genetic test and then select drugs that look to be good matches, but which are not approved for the specific cancer a patient is suffering from. The National Cancer Institute, a government agency, is trying something similar with a trial it calls MATCH. This involves sending tumour biopsies to gene-testing laboratories that then scan them for more than 4,000 possible variants of 143 pertinent genes.

Taking biopsies such as these is a routine part of cancer therapy. It, too, though, is ripe for improvement. Some tissues (blood, lymph and skin, for example) are fairly easy to get at, but many tumours are deep in the body, or in vital organs, or both. Sampling these is invasive and potentially dangerous. Researchers have therefore wondered for a long time whether something as simple as a blood test might be developed to replace such biopsy. This hope is based on the knowledge that tumours shed pieces of genetic material, known as circulating tumour DNA(ctDNA) into the bloodstream. But until recently scientific instruments have not been sensitive enough to detect ctDNA routinely and reliably.

That is now changing. So-called liquid biopsies, which will not only diagnose hard-to-get-at solid tumours but monitor the progress of their treatment, are on the verge of reality. At the meeting researchers sponsored by Guardant Health, a diagnostics company, announced the results of one of the largest liquid-biopsy studies so far.

This study looked for the ctDNA of six relevant genes in 15,000 patients suffering from one of 50 different types of tumour. The test was not perfect. Only 83% of patients had sufficient ctDNA for it to show up. But in those cases where ctDNA was detected the mutations indicated were also present in conventional biopsies between 94% and 100% of the time. The test, in other words, is reliable. Moreover, in almost two-thirds of the cases where ctDNA was detected, the results led to suggestions about how the patients involved should be treated.

If liquid biopsy can be made routine, the clinical consequences will be vast. Conventional biopsies can be both costly and slow to process. Moreover, the heterogeneity of many tumours, caused by progressive mutation over the course of time, is hard to sample by nipping out one bit of the tumour. If ctDNA is shed by all parts of a tumour, though, a liquid biopsy will be able to capture these differences. It will also be able to follow them as they progress because, unlike conventional biopsy, it can be done frequently without harming the patient. That is important. What constitutes the best treatment can change as the tumour itself changes. Many researchers therefore feel that it is only a matter of time before liquid biopsies become a standard part of therapy. They are already coming to market. Foundation Medicine, of Cambridge, Massachusetts, launched a commercial liquid biopsy in May. Qiagen, a German firm, followed suit on June 1st. Genomic Health, of Redwood City, California, says it will offer a test later this year. And Myriad Genetics, based in Salt Lake City, Utah, is also developing such tests.

Such is the excitement over liquid biopsies that some wonder if they might be used to catch cancers even before symptoms are apparent. That would be important, for the earlier a tumour is spotted, the easier it is to cure. The biggest manufacturer of DNA-sequencing machines, Illumina, based in San Diego, said recently that it would form an offshoot, Grail, to develop just such a test. The proposed test will use “ultra-deep sequencing”, a technique that reads the DNA in a sample tens of thousands of times over, in order to pick up rare signals such as that from ctDNA.

Yet one of the flaws of ctDNA is that it does not reveal where in the body a cancer is found. That is why some argue that magnetic-resonance imaging is now sophisticated enough to screen individuals for the presence of most cancers. The Health Nucleus, a firm based in San Diego, is offering full-body scans using it for just this purpose. David Karow, a clinical radiologist who works both there and at the nearby San Diego campus of the University of California, is optimistic about the technique’s potential for wider use. He has been part of a study published recently in Clinical Cancer Research that suggests MRI might become the standard method for prostate-cancer screening. His research shows that his imaging technology, RSI-MRI, can differentiate between benign lesions and tumors with high accuracy, and also between low-grade tumours, which just need to be monitored, and aggressive ones that need to be treated.

Personalised cancer treatment, long talked of, is thus now becoming real. By detecting problems earlier and getting therapies right first time, it will save lives which might otherwise be lost. Better molecular understanding of the underlying processes of cancer, meanwhile, will extend the range of lives that medicine can aspire to save. There is still a long way to go. But gradually and inexorably the appeals court of oncology is tearing up cancer’s death warrants.