New 'sneaks' to treat the most serious tumors more effectively

Geoff Macyntire and Bárbara Hernando, CNIO scientists who have participated in the research. / LML Cnio

CNIO scientists develop a biomarker that will make it possible to be more precise in the diagnosis and treatment of cancers with the highest mortality rate

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Researchers from the National Cancer Research Center (CNIO) and the Cancer Research UK Cambridge Institute have perfected a method to decipher the genetic chaos of the deadliest cancers and use this information to treat them more effectively. The work is detailed in an article published by 'Nature', one of the most prestigious scientific journals in the world. The method described in the article facilitates the detection of 'fingerprints' or 'sneaks' in the genome of tumors that allow knowing the mutational mechanism that causes tumor development and, thanks to this, makes it possible to identify the vulnerability of these tumors against which direct treatment. Knowing the genomic identity of the most aggressive cancers will enable, first, more precise diagnoses and, second, a choice of the most optimal treatment for each patient, something that until now was very difficult for these types of cancer.

The research has been co-directed by Geoff Macintyre, head of the Computational Oncology group at the CNIO, and Florian Markowetz, senior researcher at Cancer Research UK Cambridge Institute (United Kingdom), and the CNIO expert, Bárbara Hernando, and scientists from other British, Canadian, Belgian and German centres.

Researchers have analyzed the chromosomal instability of 7,880 tumor samples from 33 different types of cancer

The work focuses on deciphering the so-called 'chromosomal instability', one of the hallmarks of the most aggressive cancers. Under normal conditions, the cells of the body, by dividing, make sure that the daughter cells have the correct number of chromosomes. However, a cancer cell usually loses or gains chromosome fragments or entire chromosomes, and therefore their genomes do not have the right amount of genetic material. This genetic chaos, caused by a mechanism known as genomic instability, is detected to a greater extent in more serious cancers, those with the highest mortality figures. Therefore, higher levels of genomic instability are associated with more advanced stages of cancer, poorer prognosis for cure, metastasis, and resistance to therapies commonly used in the clinic against these aggressive tumors.

complex biological phenomenon

Chromosomal instability is a very complex biological phenomenon because it has varied causes and multiple consequences. Due to 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 the causes of this genomic instability. And that is precisely what, from now on, allows the work carried out by the CNIO researchers to do.

"Our biomarkers can predict the efficacy that therapies will have on a specific tumor"

geoff macyntire

Head of the CNIO Computational Oncology group

Research has characterized the causes, diversity, and extent of chromosomal instability associated with the most severe tumors. But the work goes much further because 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 make it possible for both the diagnosis and the chosen treatment to be much more precise.

Less effective precision medicine

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

With this graph from a chaotic 'crime scene' to a more orderly one, the scientists try to visualize what they have understood. /

Barbara Hernando

The work of the CNIO researchers eliminates this impossibility because it establishes a catalog of chromosomal instability patterns that can be identified when making the diagnosis. And each of these patterns is associated with information on its possible response to the 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 diagnosing the most aggressive tumors and, above all, when choosing the most appropriate therapy to combat them because, as Geoff Macyntire, co-director of the research, explains, "Our biomarkers can predict how effective therapies are going to be on a specific tumor." "To obtain these patterns of the different genomic chaos, -continues Macintyre- we have analyzed the chromosomal instability of 7,880 samples of tumors from 33 different types of cancer".

Creating a spin off

The group that has carried out this research has launched a company (spin off), called Tailor Bio, based in the United Kingdom and that has licensed a patent on the method described in the 'Nature' article, in addition to another patent obtained on a previous work that the team developed in the same line of work. The intention of the researchers with these steps is that this advance begins to be used in clinical practice as soon as possible.

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