Mar 18, 2026
3 min read
The CRG study reveals a new tool to measure the activity of cancer-feeding cytokines
Cancer is caused by faulty genes, but what also determines the behavior of cancer cells is the way in which gene instructions are cut and rearranged before being turned into the proteins that keep the cell alive.
A study published in Nature Communications reveals a new way to directly measure this editing process, known as splicing.This is the first time it has been possible to obtain a clear view of how tumors systematically reconfigure their genetic instructions to promote their growth and survival; this could point to new ways to control cancer.
As a proof of concept, the method was applied to biopsies of solid tumors.Approximately 120 new therapeutic targets were identified, molecules that could be up- or down-modulated to restore balance in the future cellular editing machinery.
"Instead of counting the pieces, our approach is to understand the behavior, which has allowed us to have a new way to orient ourselves in the chaotic biology of a tumor. It is early, but it offers us a much clearer map of where to look for new ways to attack the disease," says Dr.
Measure the changes made
In each cell, the genetic instructions are first copied into temporary messagesBefore those messages are used, some pieces are removed and the rest reassembledThis editing step allows a single gene to generate different messages capable of producing different proteins, an important characteristic for complex life.
Almost all cancers hijack cellular splicing, changing the way messages are cut and transported.Tumors do this to produce protein variants that allow them to grow faster, hide from the immune system or become resistant to treatments.
To understand this process, the molecules that carry out the editing, also known as splicing factors, are usually measured.But these cellular editors can be controlled in various secret ways, so that their activity can be unchanged, even if the proteins themselves are destroyed, chemically modified or moved to other parts of the cell.The result is often a confusing picture that makes it difficult to find new ways to control the disease.
A team from the Barcelona Center for Genomic Regulation and Columbia University tackled this problem by reversing the logic and editing itself rather than editors.
The researchers adapted an existing technique called VIPER to measure which bits of the gene's message were retained and which were deleted.These patterns act like fingerprints on genetic messages and reveal which editorial forces were actually active, regardless of how editors were controlled.
The technique can be used on a wide range of available RNA sequencing data.This means that it can be applied to thousands of existing models without the need for new tests.
Two hidden cancer programs
The researchers applied VIPER to nearly 10,000 tumor biopsies from 14 types of cancer from The Cancer Genome Atlas, a public database.Each biopsy was paired with healthy tissue samples for comparison.
Two major cellular programming programs have been found to occur frequently in all types of cancer.One of them acted as an accelerator, increasing its activity in tumors, with very poor clinical outcomes.The other acted as a brake, losing its potency in cancer and resulting in greater survival.
The findings suggest that cancers, despite their diversity, share common cell adaptation strategies that have remained elusive in research focused solely on genes.
When analyzing any biological feature that can tip the balance of cell-to-cancer resolution, about a hundred candidates are found.Among the most prominent is a gene called FUS, best known for its role in neurological disorders.Although it has not been studied in oncology research, its strong predictive signal indicates that it deserves more attention.
than cancer
The effects go beyond cancer.Because the technique focuses on the result of gene editing rather than the specific cause, it can be applied to many diseases in which cells change the way they gather their signals.
"We started with cancer because we had the data, but this method is useful for any disease that changes the message of cells, including neurological disorders or immune diseases," concluded Dr. Anglada Girotto.
The work was led by Miquel Anglada Girotto and Luis Serrano and Samuel Miravet-Verde at CRG.The research is based on analytical tools pioneered by Andrea Califano and her team at Columbia University.The research was funded by the European Research Council, the Spanish Ministry of Science and Innovation and the Higher Administration of Catalonia.
Anglada et al."Exon entry signatures accurately assess splicing factor activity".Nature Communications, 2026.
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