A new study, by researchers from the National Cancer Research Center (CNIO) and other international institutions, published this week in the journal Nature, provides a series of biomarkers that could make it possible to choose the optimal therapy for tumours with the highest mortality rate in a much more personalised way.
The method described in the article facilitates the detection of “fingerprints” in the genome of tumours that allow knowing the mutational mechanism that causes their development and, thanks to this, makes it possible to identify the vulnerability of these tumours against which to 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, Florian Markowetz, senior researcher at Cancer Research UK Cambridge Institute (United Kingdom), and the scientist from the Spanish centre, Bárbara Hernando, as well as researchers from other British, Canadian, Belgian and German centres.
The work focuses on deciphering the so-called chromosomal instability, one of the hallmarks of the most aggressive cancers. Under normal conditions, cells in 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 a cure, metastasis, and resistance to therapies commonly used in the clinic against these aggressive tumours.
Chromosomal instability is a very complex biological phenomenon because it has varied causes and multiple consequences. Due to this, until now, when a tumour 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 us to do the work done by the authors.
This research has characterized the causes, diversity, and extent of chromosomal instability associated with the most severe tumours. 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 tumour in depth will make it possible for both the diagnosis and the chosen treatment to be much more precise.
Being able to use 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 tumour. The problem with tumours with high chromosomal instability 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.
The team’s work eliminates this impossibility because it establishes a catalogue of patterns of chromosomal instability that can be identified when making the diagnosis.
Each one of these patterns is associated with information on its possible response to the drugs commonly used against different types of tumours and the identification of other possible pharmacological targets. This means that these patterns will serve as extremely useful oncological biomarkers for diagnosing the most aggressive tumours and, above all, when choosing the most appropriate therapy to combat them.
7,880 tumour samples from 33 types of cancer
As Macyntire, co-director of the research, explains: “Our biomarkers can predict how effective therapies are going to be on a specific tumour. To obtain these patterns of the different genomic chaos, we have analyzed the chromosomal instability of 7,880 tumour samples from 33 different types of cancer”.
The authors have set up a spin-off company called Tailor Bio, based in the United Kingdom and which has licensed a patent on the method described in the Nature article, in addition to another patent obtained on 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.