Pancreatic cancer rewrites its DNA to resist treatment, single-cell study reveals

NYU Langone researchers identify MYC and TIGIT genes as key drivers of tumour evolution, opening new therapeutic targets

By LineZotpaper AI staff

Published25 October 2026

Read Time2 min

Scientists at NYU Langone Health have mapped how pancreatic cancer constantly reshapes its genetic makeup to become more aggressive, spread, and evade treatment, using single-cell analysis of nearly half a million tumour cells. The study, published October 13 in Nature Genetics, found that blocking activity of the MYC gene can push aggressive cancer cells back toward a less dangerous state, suggesting a potential new approach to treating one of the deadliest cancers.

Researchers examined 443,451 individual cells from 62 pancreatic tumours, revealing that each tumour contains between two and 11 distinct cell populations, or clones. These clones differ in their genetic characteristics and behavior: some become resistant to chemotherapy, others gain the ability to invade tissues and metastasize.

Previous studies divided pancreatic cancer cells into classical (less aggressive) and basal (more aggressive) categories but could not explain how cells shift between states. The new work shows that genetic changes within individual tumours allow this transition, with the MYC gene showing heightened activity in the most aggressive clones. In laboratory experiments, blocking MYC activity caused basal cells to revert to the classical state and become more visible to immune cells.

"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 lead investigator Despoina Kalfakakou, PhD, a postdoctoral research fellow at NYU Grossman School of Medicine and Perlmutter Cancer Center. "These findings suggest that targeting the mechanisms underlying tumor evolution, including MYC, may help restrain the cancer's rapid progression."

The research also uncovered why pancreatic cancer often dodges immunotherapy. Certain clones showed increased activity of the TIGIT gene, linked to immune escape, along with reduced activity of PD1. This combination may explain why PD1-targeted immunotherapies have been largely ineffective against the disease.

Nearly 85 percent of pancreatic ductal adenocarcinoma patients die within five years of diagnosis. Co-senior investigator Aristotelis Tsirigos, PhD, a professor at NYU Grossman School of Medicine and director of NYU Langone's Applied Bioinformatics Laboratories, noted that clinical trials for drugs targeting MYC and TIGIT are already underway for pancreatic and other cancers.

"More broadly, our study results highlight the critical role of clonal diversity, genetic plasticity, and interactions with the tumor's microenvironment in shaping human pancreatic ductal adenocarcinoma biology," said Dr. Tsirigos.

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Analysis

Why This Matters

Pancreatic cancer is one of the deadliest cancers, with a five-year survival rate of only about 15 percent; understanding its evolution could lead to new treatments.
The single-cell approach reveals tumour complexity that bulk analysis misses, potentially improving how cancers are studied and targeted.
If MYC and TIGIT become viable drug targets, they could offer new options for patients who currently have few.

Background

Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer and is notoriously difficult to treat because it often resists chemotherapy and immunotherapy. More than half a dozen genes have been linked to the disease, but how the cancer adapts over time has been unclear. Traditional methods examine many tumour cells together, obscuring differences between cell populations. This study used single-cell transcriptomics to analyse individual cells from 62 tumours, including samples from six patients taken both before and after chemotherapy, to track how the cancer evolves in response to treatment.

What to Watch

Clinical trial results for drugs that inhibit MYC or TIGIT, which are already being tested for pancreatic and other cancers.
Larger studies that apply single-cell clonal analysis to track tumour evolution over the full course of treatment.
Potential development of therapies that target the genetic plasticity of pancreatic cancer, rather than just one mutation.

Sources

Scientists discover how pancreatic cancer rewrites its DNA to escape treatment · ScienceDaily

Checked

12 claims in this story checked against 1 source: 7 supported.

Show each claim

SupportedPancreatic cancer rewrites its DNA to resist treatment, as revealed by a single-cell study.Latest Science News -- ScienceDaily: “Scientists discover how pancreatic cancer rewrites its DNA to escape treatment.”
Partly supportedNYU Langone researchers identify MYC and TIGIT as key drivers of tumour evolution and potential therapeutic targets.Latest Science News -- ScienceDaily: “Researchers discovered that certain cancer cell clones showed increased activity of the TIGIT gene, which is associated with proteins that help tumors escape immune detection.”
SupportedKalfakakou said: “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. These findings suggest that targeting the mechanisms underlying tumor evolution, including MYC, may help restrain the cancer's rapid progression.”Latest Science News -- ScienceDaily: “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. “These findings suggest that targeting the mechanisms underlying tumor evolution, including MYC, may help restrain the cancer’s rapid progression.”
SupportedTsirigos said: “More broadly, our study results highlight the critical role of clonal diversity, genetic plasticity, and interactions with the tumor's microenvironment in shaping human pancreatic ductal adenocarcinoma biology.”Latest Science News -- ScienceDaily: “More broadly, our study results highlight the critical role of clonal diversity, genetic plasticity, and interactions with the tumor’s microenvironment in shaping human pancreatic ductal adenocarcinoma biology,” said Dr. Tsirigos.”
SupportedThe study was published October 13 in Nature Genetics.Latest Science News -- ScienceDaily: “Published on October 13 in Nature Genetics, the study identified several genetic changes associated with pancreatic cancer progression.”
SupportedResearchers examined 443,451 individual cells from 62 pancreatic tumours.Latest Science News -- ScienceDaily: “the scientists examined gene activity (using transcriptomics) in 443,451 individual cells collected from 62 tumors”
Partly supportedEach tumour contains between two and 11 distinct cell populations, or clones.Latest Science News -- ScienceDaily: “individual tumors contained approximately two to 11 distinct clones”
SupportedIn laboratory experiments, blocking MYC activity caused basal cells to revert to the classical state and become more visible to immune cells.Latest Science News -- ScienceDaily: “In additional laboratory experiments, the researchers blocked MYC activity in aggressive basal pancreatic cancer cells. Remarkably, the cells shifted back toward the less aggressive classical state. The change also made the cancer cells more exposed to immune cells”
Partly supportedThe most aggressive clones showed heightened MYC activity.Latest Science News -- ScienceDaily: “One particularly important finding involved MYC, a gene that showed heightened activity in some of the most aggressive cancer cell populations.”
Partly supportedCertain clones showed increased TIGIT activity and reduced PD1 activity, a combination that may explain why PD1-targeted immunotherapies have been largely ineffective.Latest Science News -- ScienceDaily: “At the same time, these clones exhibited reduced activity of the PD1 gene. This combination may help explain why immunotherapies designed to target PD1 have shown limited effectiveness against pancreatic cancer.”
SupportedNearly 85 percent of pancreatic ductal adenocarcinoma patients die within five years of diagnosis.Latest Science News -- ScienceDaily: “Nearly 85 percent of patients die within five years of being diagnosed.”
Partly supportedClinical trials for drugs targeting MYC and TIGIT are already underway for pancreatic and other cancers.Latest Science News -- ScienceDaily: “clinical trials investigating drugs that inhibit MYC or TIGIT are already underway for pancreatic ductal carcinoma and other cancers.”

Correction

25 October 2026An earlier version of this story described Aristotelis Tsirigos as co-director of NYU Langone's Applied Bioinformatics Laboratories. He is the laboratories' director.