Scientists have developed a new test that can reveal when cancer began and how quickly it is progressing, helping doctors predict when treatment will be needed.
Diego Mallo, a researcher with the Biodesign Center for Biocomputing, Security and Society at Arizona State University, joins a study led by the Institute of Cancer Research, London, and the Hospital Clinic-IDIBAPS Biomedical Research Institute of Barcelona, Spain. Their findings, published Wednesday in the journal Nature, introduce a novel technique to track the evolutionary history of a tumor from a single sample.
The new technique, which involves analyzing subtle changes in tumor DNA called methylation, has been tested successfully on different types of blood cancer. The team hopes that it can work across many types of cancer, offering the prospect of better prediction of disease progression and ongoing monitoring, reducing the need for repeated, invasive biopsies.
“Usually, we study the evolution of cells from normal function to cancer using DNA mutations. These new methylation markers provide more information for a fraction of the cost since they accumulate faster,” Mallo says. “The fact that evolutionary parameters estimated using this method are strong predictors of the cancer’s outcome shows their power to improve both cancer management and monitoring patients at risk.”
Decoding tumor growth with DNA barcodes
Cancer grows and spreads by evolving, where the cells mutate and change. Understanding how this process works can help predict how a patient’s disease might progress for cancer types when treatment isn’t given immediately. It can also predict how an individual might respond to treatment.
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Some precancerous conditions or early-stage cancers may not require immediate treatment but do need regular monitoring. They include some blood cancers, low-grade prostate cancers, inflammatory bowel disease, Barrett’s esophagus and some low-grade gliomas.
To test the hypothesis, researchers looked at methylation marks — chemical modifications on the DNA of cancer cells.
Recently, members of this team as part of the Arizona Cancer Evolution Center, co-directed by Biodesign researcher Carlo Maley, found that a set of methylation marks act like a “barcode” for each cancer cell, helping researchers trace the “family tree” of a tumor. They discovered that the way a cancer has evolved predicts how it will act going forward.
In this new study, a mathematical model called EVOFLUx was developed to read the barcodes and reconstruct the tumor’s evolutionary history from the tumor sample.
The team used EVOFLUx to analyze DNA methylation data from over 2,000 patients with various types of blood cancers, including both aggressive and slow-growing diseases that occur in both infants and older adults, and samples from different stages of disease and treatment.
Their findings showed that each patient’s cancer has a unique evolutionary history. Some cancers had been growing in the body for more than a decade before they were first detected, whereas other cancers grew very rapidly in just a few months.
Evolution as a guide to leukemia care
Chronic lymphocytic leukemia (CLL) is a type of cancer that usually develops very slowly and does not always need to be treated straight away. EVOFLUx accurately detected faster-growing CLL tumors and predicted that patients with them would need treatment sooner and had a shorter overall survival time. These patients had nearly four times the risk of needing treatment sooner and had about 1.5 times the risk of their cancer being fatal.
“Some CLL patients suffer a complication — Richter transformation — whereby some CLL cells become more aggressive,” Mallo says. “I developed the program we needed to use multiple samples per patient in a smaller patient cohort, which allowed us to discover that the cells that originated this transformation split from the regular CLL cells decades before their presentation in all cases.”
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The researchers also noted that acute lymphoblastic leukemia (ALL), which is a fast-growing cancer in young children, tends to be “evolutionarily younger” compared with other blood cancers. This means the cancer cells had undergone fewer divisions and accumulated fewer changes over time. The rapid growth helps explain why ALL often needs urgent treatment.
However, the study also observed highly variable growth rates of ALL, which may help clinicians predict which children will benefit most from treatment.
The new method uses low-cost DNA methylation testing, which is widely available, making it cost effective and suitable for use on a large scale. The scientists say the next steps will be to demonstrate, in clinical trials, how well the predictions work.
“In our quest to develop these evolutionary biomarkers of cancer progression, we have already extended our methods to increase the number of evolutionary parameters they estimate and are using them to study premalignant conditions.”
Understanding how cancer evolves, adapts and resists treatment is key to managing it. This research offers new insights into predicting how a patient’s cancer will progress and tracking its changes over time — without repeated, invasive biopsies. In the future, these findings could help drive more personalized and effective treatments, even for cancers resistant to today’s therapies.
This research received funding from Cancer Research UK, the Spanish Association Against Cancer, the U.S. National Institutes of Health, The La Caixa Foundation and the European Research Council.