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An analysis of nearly half a million cells from dozens of patients' tumors reveals how cancer cells continuously reshape their genetic makeup over time, enabling them to evade treatment for one of the deadliest forms of cancer.

Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the study focused on pancreatic ductal adenocarcinoma, an often difficult-to-treat disease known to kill nearly 85% of people within five years of diagnosis.

While more than half a dozen genes have been implicated in the complex disease, the analysis of single tumor cells provided new insights into how subpopulations of pancreatic cancer cells reconfigure their DNA within tumors over time.

The team's analysis revealed a diverse set of clones, or clusters of tumor cells that have a similar genetic makeup. These clones showed striking differences in behavior, with some evolving to resist therapy and others acquiring the ability to spread rapidly. The findings suggest that ongoing reshaping of the cancer cells' DNA fuels both treatment resistance and metastasis.

Past research analyzing bulk groups of pancreatic cancer cells had focused on separating them into two subtypes—classical (less aggressive) and basal (more aggressive). However, the research could not explain how cancer cells shift between these subtypes. The new findings show that genetic reconfiguration within a tumor enables cancer cells to transition between subtypes.

Published online Oct. 13 in the journal Nature Genetics , the new study identified specific genetic changes that emerge during tumor evolution, including increased activity of the MYC gene in aggressive tumor cell populations.

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