A historic discovery allows us to predict the evolution of cancer.

Photo of National Cancer Institute in Unsplash

An unprecedented discovery in biomedical research could transform the way cancer is diagnosed and treated. Scientists from the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) in Barcelona and the Institute of Cancer Research in London have deciphered the evolutionary trajectory of tumors, paving the way for predicting how the disease will progress.

The study, published in the journal Nature, demonstrates that cancer evolution depends largely on the epigenome, i.e., epigenetic marks on DNA, and in particular on fluctuating methylation. Researchers have identified a "methylation signature" in the original cell that gave rise to the tumor, which would allow them to reconstruct its entire evolutionary history and predict its future aggressiveness.

The key to this breakthrough is EVOFLUx, an algorithm trained on nearly 2,000 patients with different types of leukemia and lymphoma. This tool uses methylation fluctuations at specific DNA sites (fCpGs) to create a true "evolutionary barcode" of the tumor. This makes it possible to determine parameters such as growth rate, tumor age, and clonal diversity.

The findings show notable differences between tumors: the most aggressive childhood leukemias, for example, had a growth rate of 44.3 cell divisions per year, compared to 11.7 in other subtypes. In the case of chronic lymphocytic leukemia (CLL), tumor progression independently predicted both time to first treatment and overall survival, even considering classic factors such as IGHV or TP53 mutations.

EVOFLUx: Success stories in cancer studies

“Evolutionary histories are independent prognostic factors,” the authors note, further emphasizing that most lymphoid cancers evolve in an “effectively neutral” manner, with no dominant subclones for much of their history. Only in a few cases were subclones with selective advantages detected, providing new insights into treatment resistance and relapse.

With this breakthrough, the scientists compare the method to an airplane's black box, which records all the data from a flight: "For the first time, we can trace the entire trajectory of a tumor from its cell of origin," they explain.

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Sources:

• Infobae
• Nature