Researchers developed a new method to predict how cancer cells evolve by gaining or losing whole chromosomes.
Chromosome changes create rapid shifts that help tumors grow, adapt and resist treatment.
The new tool, called ALFA-K, maps how favorable or harmful chromosome changes are in different cancer cells.
The study quantifies how whole-genome doubling helps cancer cells survive high levels of chromosomal instability.
Findings lay the groundwork for evolution-aware approaches to cancer treatment.
TAMPA, Fla. (Jan. 22, 2026) — Researchers at Moffitt Cancer Center have developed a new way to predict how cancer cells evolve by gaining and losing whole chromosomes, changes that help tumors grow, adapt and resist treatment.
In a study published in Nature Communications, scientists describe a computational approach called ALFA-K that uses longitudinal, single-cell data to reconstruct how cancer cells move through different chromosome states over time and identify which configurations are favored by evolution.
The findings show that cancer evolution is not random. Instead, tumors follow measurable rules shaped by chromosome configuration, evolutionary dynamics and treatment-related stress, offering a new framework for anticipating how cancers change and respond to therapy.
Q&A with Noemi Andor, Ph.D., corresponding author and associate member in the Integrated Mathematical Oncology Program at Moffitt.
What problem were you trying to solve with this research, and why does it matter for understanding cancer?
Cancer evolves. As tumors grow, their cells constantly make mistakes when copying and dividing their DNA. Many of those mistakes involve gaining or losing whole chromosomes. This creates a mix of cancer cells with different chromosome combinations inside the same tumor.
The problem was that researchers had no reliable way to determine which of those combinations help cancer cells survive. The number of possible chromosome states is enormous, and most existing approaches could only capture snapshots in time or average behavior across many cells.
ALFA-K was developed to solve this problem by using longitudinal, single-cell data to reconstruct how cancer cells move through chromosome states over time and which states are favored by evolution. Without that understanding, cancer progression and treatment resistance can appear unpredictable. Our work shows they follow measurable rules.
Why are chromosome changes so important for tumor growth and treatment response?
Chromosomes contain hundreds or thousands of genes. When a cancer cell gains or loses a chromosome, it changes the dosage of many genes at once. This can immediately alter how the cell grows, divides or responds to stress.
These changes allow cancer cells to make large evolutionary jumps rather than small adjustments. They also create diversity within a tumor, which increases the chances that some cells survive treatment.
Importantly, the effects of these changes depend on a cell’s existing chromosome makeup. The same chromosome change can be helpful in one context and harmful in another. This context dependence helps explain why cancer evolution has been so difficult to predict.
How is ALFA-K different from previous tools, and what does it allow researchers to do?
Before ALFA-K, chromosome changes were often assumed to have fixed effects. Researchers sometimes treated gaining or losing a chromosome as always beneficial or always harmful. Real cancer evolution is more complex.
ALFA-K tracks thousands of individual cells over time, accounting for ongoing chromosome instability and reconstructs local fitness landscapes. These landscapes describe how advantageous or harmful a chromosome change is given a cell’s current chromosome configuration.
The tool also shows that the rate of chromosome errors matters. When chemotherapy increases chromosome mis-segregation, cancer cells move across these landscapes more quickly. Depending on the landscape’s shape, this can push tumors toward chromosome states that are more tolerant of instability.
In this study, ALFA-K estimated the fitness of more than 270,000 distinct chromosome configurations. This made it possible to ask questions that were previously inaccessible.
What does whole-genome doubling mean, and why is it an important finding?
Whole-genome doubling occurs when a cell copies all of its chromosomes. Previous research showed that this can help cancer cells survive, but there was no way to measure how much protection it provides.
ALFA-K allows researchers to quantify that buffering effect. The method measures how much more tolerant genome-doubled cells are to chromosome mistakes compared with non-doubled cells.
This matters because buffering is not all or nothing. There is a threshold at which genome doubling becomes advantageous. By quantifying that threshold, ALFA-K turns genome doubling from a descriptive observation into a predictable evolutionary event.
How could this research eventually help guide cancer treatment?
ALFA-K shifts cancer research from describing what tumors look like to predicting how they will evolve.
In the future, this approach could help doctors interpret repeat biopsies, identify when a tumor is approaching a dangerous evolutionary transition and choose treatments that limit cancer’s ability to explore harmful chromosome configurations.
The long-term goal is evolution-aware cancer therapy. This approach aims to anticipate how tumors will change rather than reacting after resistance has already emerged.
This study was supported by the National Cancer Institute (1R37CA266727-01A1, 1R21CA269415-01A1, 1R03CA259873-01A1).
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 58 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt’s expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, X, Instagram and YouTube.
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