Personalizing Cancer Treatments Could Lead to Better Results

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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. 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 tumors 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 personalized medicine.

Picking winnersThese days cancer is seen less as a disease of specific organs and more as one of the 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 tumors 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. 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 tumor of a patient with his treatment.

Using it caused tumors 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 organization in its own right it has decided to run a clinical trial to look at personalized 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 tumor biopsies to gene-testing laboratories that then scan them for more than 4,000 possible variants of 143 pertinent genes. The heterogeneity of many tumors, caused by progressive mutation over the course of time, is hard to sample by nipping out one bit of the tumor.

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. Better molecular understanding of the underlying processes of cancer will extend the range of lives that medicine can aspire to save.

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