New war against cancer will be in the genes

In the 1970s, scientists began to reveal the true face of cancer. It was discovered that many tumors arise due to genetic defects within normal cells. Harold Varmus, one of the leaders of that revolution, described the disease as a deformed version of ourselves. Since then, researches have uncovered a tremendously diverse disease with fearsome adaptability. The total victory in the war against cancer launched in those years seemed impossible.

But the study of these diseases not only produced overwhelming knowledge. Molecular information on tumors allowed the design of the first drugs to be controlled. Faced with chemotherapy, which attacks all cells and do not damage the cancerous, they began to create drugs for specific mutations behind specific types of cancer. Along with these new drugs, diagnostic tests also appeared that allowed to know if the patient had a specific mutation that would make him respond well to that treatment.

Last week Boston became the center of another revolution. Improvements and cheaper sequencing techniques, the emergence of new treatments for specific mutations and the increase in data management capacity offer the opportunity to use the vast accumulated information to better combat cancer.

Garret Hampton, vice president of Roche’s biomarkers development section, the drugmaker and the world’s leading cancer drug producer in 2015, recalled how it is now known that even though two-person cancer have the same appearance under the microscope may be very different from the molecular point of view. This new approach increasingly causes cancer to be treated as a disease that depends on genetic errors rather than an organ-associated disease. In this way, a drug used against a mutation that affects breast cancer could be used to treat a gastric cancer in which that same genetic change is also found. One example is trastuzumab, a molecule approved in 1998 to treat breast tumors with the HER2 gene overexpressed, which twelve years later was given the go-ahead to treat gastric cancer.

This is the further step in personalized cancer treatment. Instead of looking for the most likely mutations for a cancer type, as is often done now, they have the ability to dig up 315 genes related to the development of cancer. In this way the test is agnostic, because it does not require oncologists to make a bet on what kind of mutations they believe they can find. In addition, it allows much more information to be obtained from patients’ biopsies, scarce and difficult to obtain cancer specimens.

Once the mutations have been identified, the information is crossed with the one in their database of about 100,000 patients. So they try to learn what worked on other occasions, rare cases included, to design the best combination of drugs for the combination of patient mutations. This system has its version for solid and hematological tumors, and includes a liquid biopsy, a way to detect some types of cancer through the DNA that they release into the bloodstream. On the one hand, more evidence is needed about the clinical benefit of treating cancer with personalized medicine versus conventional treatments. However, the researchers cite an analysis of 570 phase II clinical trials with more than 32,000 patients where a statistically significant benefit of more than three months of progression-free survival was observed in those patients who were treated on the basis of molecular alterations that allowed them to direct their treatment.

The way in which the cancer’s molecular profile of the patients can prolong their lifes has yet to be better analyzed. The scientists are clear that there are molecular determinants that prolong the lives of patients, but they do not know if they will benefit globally or not.

Another difficulty, related to the previous point, is the cost of the product, something higher than $ 5,000. Conventionally, patients receive a series of treatments depending on the type of cancer that is detected and new drugs are tested with a high component of trial and error. It is possible that when the usual drugs do not work and the patient is running out of options, the possibility of performing an analysis may be considered. In long run, investing in this test will initially lower the costs of treatment because it would avoid giving the patient drugs at a very high cost that is not known if they will work. In any case, the accumulation of scientific evidence would serve to raise the funding of this type of evidence.

Genetic profiles are also being used to better design clinical trials in which the personalized drugs of the future are being tested. With them, patients can be better chosen for these experiments and would, according to the company’s managers, be another way of reducing the production of new products. This aspect is very relevant, because one of the great problems of personalized medicine is its cost. A drug may have very good results, but that simply can not be paid.