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Scientists have found a way to identify and interpret “signatures” that reveal the complex genetic causes of some of the deadliest cancers, which often have a survival rate of less than 10%. The results, published in “Nature”, could allow them to develop more precise treatments and significantly improve survival rates.
Scientists now use individual genetic changes to develop mutational signatures, which can be used to understand the origin of a cancer and predict how a cancer progresses. However, until now, there has been no framework to interpret the larger and more complex patterns of genetic changes seen in chromosome instability in the same way.
Our genetic code is stored on 23 pairs of chromosomes, the “strands” that make up the genome.
But when our genome is copied, these chromosomes can become unstable and DNA segments can be duplicated, deleted, or rearranged.
Chromosomal instability is a common feature of cancer, occurring in about 80% of tumors, but this jumble of fragments can be difficult to read, making it difficult to understand exactly what types or “patterns” of instability are present in a tumor certain. Instead, tumors are divided into broad categories that have high or low amounts of chromosome instability.
Cancers with high levels of chromosomal instability are extremely deadly and often have survival rates of less than 10%. As such, understanding and treating chromosomal instability it is critical to improving outcomes for millions of cancer patients around the world.
Now, for the first time, scientists from the University of Cambridge and the National Cancer Research Center (CNIO) have published a robust framework that allows them to analyze chromosomal instability in human cancers.
Florian Markowetz and colleagues investigated patterns of chromosome instability in 7,880 tumors, representing 33 cancer types, including liver and lung cancer, from The Cancer Genome Atlas. By analyzing the differences in the number of DNA sequence repeats within the tumors, they were able to characterize 17 different types of chromosome instabilitya. These chromosomal instability signatures were able to predict how tumors might respond to drugs, as well as help in the identification of future drug targets.
This research has led to the formation of Tailor Bio, a company spin-off from the Cancer Research UK Cambridge Institute, whose goal is to build a new platform for precision medicine against cancer. This platform will allow the team to develop better drugs for a wide variety of cancer types and to group patients according to their cancer type more precisely, ensuring that they receive the best and most targeted treatment for their tumor.
Markowetz, a senior group leader at the UK’s Cambridge Institute of Cancer Research, points out that “the more complex are the genetic changes that underlie a cancer, the more difficult they are to interpret and the more challenging it is to treat the tumor. This is tragically clear from the very low survival rates for cancers that arise as a result of chromosomal instability.”
“Our discovery offers hope that we can change things, bringing much more sophisticated and precise treatments. With Tailor Biowe are now working to bring our technology to patients and develop it to a level where it can transform patients’ lives.”
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 chromosome instability it is that they did not allow this type of medicine to be used effectively because in them there is not a single “defective” gene but many.
This work 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.”
Tailor Bio, based in the United Kingdom, 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.
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