Cancer Cells' Ability to Adapt Could Yield New Treatment Approaches

Study reveals how pancreatic cancer cells regulate autophagy to survive or grow

Published on Feb. 18, 2026

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A new study led by NYU Langone Health researchers shows that pancreatic cancer cells' ability to detect the extracellular matrix (ECM) surrounding them determines whether they focus on rapid growth or enter a protective 'self-eating' state of autophagy to survive chemotherapy. The findings suggest targeting both ECM sensing and lysosomal function could provide more effective and lasting antitumor responses.

Why it matters

Pancreatic cancer is one of the deadliest forms of cancer, with a 5-year survival rate of only 10%. Understanding how cancer cells adapt to their environment is crucial for developing more effective treatments that can overcome the disease's resistance to current therapies.

The details

The study found that pancreatic cancer cells can toggle between states of rapid growth and protective autophagy based on their ability to detect the ECM fibers around them. Cells that are in close contact with the ECM have low autophagy levels and grow quickly, while cells further from the ECM increase autophagy to survive. Genetically suppressing the ECM-sensing protein integrinα3 forced more cells into the high-autophagy state, making them more vulnerable to autophagy-blocking drugs like hydroxychloroquine. Knocking out the NF2 protein, which inhibits the integrinα3 signal, also drastically reduced tumor growth by inhibiting both autophagy and other survival pathways.

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

The players

NYU Langone Health

A fully integrated health system and academic medical center that consistently achieves some of the lowest mortality rates in the nation.

Mohamad Assi, PhD

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

Alec C. Kimmelman, MD, PhD

An author on the study and a listed 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, Department of Radiation Oncology, NYU Langone

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, might provide longer-lasting antitumor responses.

The takeaway

This study reveals a new mechanism by which pancreatic cancer cells adapt to their microenvironment, highlighting the importance of targeting both cell growth and survival pathways to overcome the disease's resistance to current treatments.