Researchers have identified how distinct populations of pancreatic cancer cells alter their genetic makeup and gene activity over time to evade medical therapies and spread throughout the body. Led by scientists at NYU Langone Health and its Perlmutter Cancer Center, the study examined pancreatic ductal adenocarcinoma (PDAC), the most common and lethal form of the disease. Published in the journal Nature Genetics on October 13, 2026, the research maps how individual tumor cells transition between less aggressive and more aggressive states, while highlighting a specific gene that could serve as a target for future drug development.

Pancreatic ductal adenocarcinoma remains one of the most challenging malignancies to treat in modern oncology. Nearly 85 percent of patients die within five years of receiving a diagnosis, according to ScienceDaily, while coverage in the San Diego Union-Tribune characterizes the five-year mortality rate as exceeding 85 percent. Although previous research has linked more than half a dozen genes to the disease, scientists have struggled to explain how these tumors rapidly adapt to survive chemotherapy and immune system attacks.

Mapping Genetic Diversity Inside Individual Tumors

Historically, laboratory studies of pancreatic cancer analyzed large collections of tumor cells grouped together. Those bulk measurements allowed scientists to divide pancreatic cancer cells into two main categories: a less aggressive "classical" state and a more aggressive "basal" state. However, looking at cells in bulk obscured how individual cells shift from one category to the other as the disease advances.

To capture a cell-by-cell view, the research team used transcriptomics, a technique that measures gene activity across individual cells. The investigators profiled 443,451 single cells collected from 62 tumors. Reporting on the exact patient cohort size varies slightly: according to SciTechDaily and ScienceDaily, the 62 tumors came from 56 men and women, whereas the San Diego Union-Tribune reports that the samples were gathered from 59 people. Within the participant group, six patients provided tumor samples both before and after undergoing chemotherapy, offering the team a direct, though limited, view of how treatment pressure correlates with cellular changes.

By tracing patterns of gene activity and variations in DNA copy numbers—which refers to the number of copies of a particular gene present in the genome of a cell—the team discovered that individual pancreatic tumors are not uniform masses. Instead, each tumor contains between two and 11 distinct cell populations, known as clones, on average. Each clone consists of cells sharing similar genetic characteristics, and individual tumors house varying mixtures of classical and basal cells.

As the cancer progresses, these clonal populations behave differently. Some clones acquire genetic changes and copy-number variations that allow them to withstand cancer treatments, while others develop traits that help them invade surrounding tissues and metastasize to distant organs.

"Our study provides the most granular view to date of pancreatic ductal adenocarcinoma, revealing how ongoing genetic reshaping drives tumor evolution over the course of disease," said study lead investigator Despoina Kalfakakou, PhD, a postdoctoral research fellow at NYU Grossman School of Medicine and Perlmutter Cancer Center.

Targeting the MYC Gene in Laboratory Models

In addition to mapping how tumors evolve, the researchers examined which specific genes were most active during the transition toward aggressive behavior. They identified heightened activity in a gene called MYC within some of the most aggressive basal cancer cell populations.

To test whether this gene directly controlled the cells' aggressive state, the team conducted laboratory experiments in which they blocked MYC activity in basal pancreatic cancer cells. Following the inhibition of MYC, the aggressive basal cells shifted back toward the less dangerous classical state. Blocking the gene also made the cancer cells more visible to immune cells, suggesting that slowing down MYC might help the body's natural defenses recognize and attack the tumor.

The analysis also uncovered clues regarding why standard immunotherapies often struggle against pancreatic cancer. In certain tumor-cell clones, researchers observed increased activity in an immune-related gene called TIGIT alongside decreased activity in another gene known as PD1. Many existing immunotherapy drugs are designed to target the PD-1 pathway; the reduced PD1 activity and elevated TIGIT activity in these specific clones may help explain how pancreatic tumors escape immune detection and resist PD-1-targeted treatments.

What This Means for Patients and Future Treatments

While descriptions of cancer "rewriting its DNA" are often used as shorthand for these findings, the study specifically points to natural genetic diversity, DNA copy-number variations, and shifting gene-activity states within tumor cell populations rather than intentional genome editing by the tumor. Understanding this ongoing cellular evolution gives scientists a clearer framework for designing future therapies.

"Our research also suggests that single-cell clonal analysis offers a better approach to understanding complex cancers, like pancreatic ductal adenocarcinoma, as it develops over time, by mapping how tumors evolve and adapt at each stage of disease progression," said study co-senior investigator Aristotelis Tsirigos, PhD, a professor in the Departments of Medicine and Pathology at NYU Grossman School of Medicine and a member of Perlmutter Cancer Center.

For patients and families affected by pancreatic cancer, it is important to note that the MYC blocking experiments and the TIGIT and PD1 observations are preclinical laboratory findings. They do not represent an immediately available treatment or a demonstrated clinical benefit in humans. Furthermore, because pre- and post-chemotherapy samples were collected from only six patients, larger clinical studies will be required to confirm exactly how chemotherapy shapes clonal evolution over time. Even so, identifying MYC and specific immune evasion pathways gives pharmaceutical researchers concrete targets to test in animal models and eventual human clinical trials.

Frequently Asked Questions

What does "DNA rewriting" mean in the context of this study?

The phrase refers to ongoing genetic reshaping within a tumor, including variations in DNA copy numbers, shifts in gene activity, and the growth of distinct cell groups (clones) over time. It does not mean that cancer cells deliberately edit their own genetic code, but rather that genetically diverse cell populations adapt and change states as the disease progresses.

Can blocking the MYC gene cure pancreatic cancer in patients today?

No. The experiments showing that MYC inhibition shifts aggressive basal cells back into a less aggressive classical state were conducted in laboratory settings. Additional testing in animal models and human clinical trials is necessary to determine if targeting MYC is safe and effective for patients.

How might these findings affect immunotherapy for pancreatic cancer?

The researchers found that certain pancreatic tumor clones have lower PD1 gene activity and higher TIGIT gene activity. This pattern offers a potential clue as to why standard PD-1-targeted immunotherapies have had limited success in pancreatic cancer, and it may guide scientists to investigate alternative or combined immunotherapy approaches in future studies.

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