They develop a biomarker that will effectively treat the most serious cancers.

A new study, published this week in the journal Natureprovides a series of biomarkers that can make it possible to choose the ideal therapy for the tumors with the highest mortality rate in a much more personalized way.

The method described in the article facilitates the detection of “fingerprints” in the genome of tumors that make it possible to know the mutational mechanism that causes their development and, thanks to this, makes it possible to identify the vulnerability of these tumors against which to direct the treatment.

Knowing the genomic identity of the most aggressive cancers will allow, firstly, more accurate diagnoses and, secondly, the choice of the most optimal treatment for each patient, something that until now was very difficult for these types of cancer.

The research was co-directed by Geoff Macintyrehead of the Computational Oncology group at CNIO, and florian markowetzsenior researcher at Cancer Research UK Cambridge Institute (UK), and scientist at the Spanish center, Bárbara Hernandoas well as researchers from other British, Canadian, Belgian and German centers.

The work is focused on deciphering the call chromosomal instability, one of the characteristics of the most aggressive cancers. Under normal conditions, the cells of the body, when dividing, ensure that the daughter cells have the correct number of chromosomes. However, a cancer cell often loses or gains chromosomal fragments or entire chromosomes, and therefore their genomes do not have the right amount of genetic material.

East genetic chaoscaused by a mechanism known as genomic instability, is detected to a greater extent in more severe cancers, those with the highest mortality rates. Therefore, higher levels of genomic instability are associated with more advanced stages of cancer, worse prognosis of cure, metastasis and resistance to therapies commonly used in the clinic against these aggressive tumors.

Chromosomal instability is a very complex biological phenomenon, as it has varied causes and multiple consequences. Because of this, until now, when a tumor is detected, the clinical diagnosis is limited to indicating whether it has high or low chromosomal instability, but does not analyze the extent or causes of this genomic instability. And that is precisely what, from now on, allows the work of the CNIO researchers.

The research characterized the causes, diversity and extent of chromosomal instability associated with the most severe tumors. But the work goes much further, as it relates each different type of chromosomal instability with the characteristics that the disease presents in cancer patients. Knowing each specific tumor in depth will allow both the diagnosis and the chosen treatment to be much more accurate.

Being able to use precision medicine

Currently, the most advanced treatment for cancer is based on the so-called precision medicine which allows the choice of therapy adjusted to the genetic and molecular characteristics of each patient’s tumor. The problem with tumors with high chromosomal instability is that they have not allowed this type of drug to be used effectively because there is not a single ‘defective’ gene in them, but many.

The authors’ work eliminates this impossibility because it establishes a catalog of patterns of chromosomal instability that can be identified at the time of diagnosis.

Each of these patterns is associated with information about its possible response to drugs commonly used against different types of tumors and the identification of other possible pharmacological targets. Which means that these patterns will serve as extremely useful oncological biomarkers for the diagnosis of the most aggressive tumors and, above all, for choosing the most appropriate therapy to combat them.

7,880 tumor samples from 33 types of cancer

As Geoff Macyntire, co-director of the research, explains: “Our biomarkers can predict the effectiveness of therapies in a specific tumor. To obtain these patterns of the different genomic chaos, we analyzed the chromosomal instability of 7,880 tumor samples from 33 different types of cancer.”

The group that carried out this research created a spin-off called Tailor Bio, based in the United Kingdom, which licensed the patent for the method described in the article by Nature, in addition to another patent obtained in previous works that the team developed in the same line of work. The researchers’ intention with these steps is that this advance begins to be used in clinical practice as soon as possible.