Study Reveals How Pancreatic Cancer Cells Adapt to Survive Chemotherapy

Researchers find cancer cells can toggle between rapid growth and treatment resistance based on their environment

Published on Feb. 17, 2026

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A new study led by researchers at NYU Langone Health has revealed that pancreatic cancer cells can adapt to their surroundings, switching between rapid growth and increased resistance to chemotherapy. The study found that the cancer cells' ability to detect the extracellular matrix (ECM) that surrounds them determines whether they focus on multiplying quickly or entering a "self-eating" survival mode known as autophagy, which protects them from treatments targeting fast-dividing cells.

Why it matters

This discovery provides important insights into the challenges of treating pancreatic cancer, which is notoriously difficult due to the cancer cells' ability to adapt and survive. The findings suggest that targeting both the ECM-mediated regulation of autophagy levels and lysosomal function in cancer cells could lead to more effective and longer-lasting treatments.

The details

The researchers grew clusters of pancreatic cancer cells in 3D spheres embedded in gel-like substances to mimic how tumors grow in the body. They found that the distance of the cancer cells from the ECM creates two distinct populations within the same tumor - one group that detects the ECM and has low autophagy levels and high growth rates, and another population more distant from the ECM that has high autophagy levels and can better survive chemotherapy. Genetically suppressing a protein called integrin subunit α3, which allows the cancer cells to detect the ECM, forced nearly all the cells into their high-autophagy mode and made them more vulnerable to autophagy-blocking drugs.

  • The study was published online on February 16, 2026 in the journal Cell.

The players

NYU Langone Health

A fully integrated health system that consistently achieves some of the lowest mortality rates in the nation, ranked No. 1 out of 118 comprehensive academic medical centers by Vizient Inc. for four years in a row.

Mohamad Assi, PhD

The first author of the study and a postdoctoral fellow in the Department of Radiation Oncology at NYU Langone.

Alec C. Kimmelman

A contributing author on the study and listed as an inventor on a patent targeting alanine transport and the autophagic control of iron metabolism. He is also on the scientific advisory board of Rafael/Cornerstone Pharmaceuticals and has been a consultant for Deciphera and AbbVie.

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What they’re saying

“Our findings show that the sensing of the ECM by pancreatic cancer cells enables them to switch between states of active growth and autophagic survival”

— Mohamad Assi, PhD, postdoctoral fellow in the Department of Radiation Oncology at NYU Langone (Mirage News)

What’s next

The researchers say that current strategies designed to block autophagy are effective for a short time, but then fail as cancer cells adapt. They suggest that targeting both the ECM-mediated regulation of autophagy levels and lysosomal function in cancer cells could provide longer-lasting antitumor responses.

The takeaway

This study highlights the remarkable adaptability of pancreatic cancer cells, which can toggle between rapid growth and treatment resistance based on their surrounding environment. Understanding these mechanisms is crucial for developing more effective and durable therapies to combat this deadly form of cancer.