Could K17 be a Key Treatment Target for Pancreatic Cancer

Study published in Cancer Research demonstrates the protein causes chemoresistance

STONY BROOK, NY, May 20, 2026 - A national team of cancer researchers led by Drs. Kenneth Shroyer and Natalia Marchenko at Stony Brook Medicine, and Dr. Luisa Escobar-Hoyos of Yale School of Medicine, investigated the role of Keratin 17 (K17) in the most common form of pancreatic cancer. They discovered that the protein is a key driver for chemoresistance to gemcitabine, an agent that is often used to treat a wide range of cancers, including advanced tumors of the pancreas, lungs and breast. Their findings highlight K17 as a potential target for the development of novel treatments to address the most aggressive forms of cancer.

Their paper, published in Cancer Research, a premier journal of the American Association for Cancer Research, explains how they uncovered the mechanisms through which K17 drives chemoresistance.

In recent years, the Shroyer/Marchenko/Escobar-Hoyos team and many other cancer researchers have determined that the expression of K17 in pancreatic and other types of cancer is associated with shorter patient survival. Beyond serving as a structural protein during embryologic development, K17 is re-expressed in many types of cancer and impacts multiple hallmarks of cancer, including cell growth, invasion and chemoresistance.

This study used cancer cell lines and tissue from human and mouse pancreatic ductal adenocarcinomas (PDACs), particularly from the most aggressive "basal" molecular subtype of the disease.

"A better understanding of the underlying molecular mechanisms driving this aggressive pancreatic cancer subtype is necessary for the development of effective therapies," explains Dr. Shroyer, Chair of the Department of Pathology in the Renaissance School of Medicine (RSOM) at Stony Brook University and a co-senior author. "We showed that K17 enters the mitochondria of the cells to stabilize dihydroorotate dehydrogenase (DHODH), a key enzyme used to build pyrimidines, one of the key building blocks of DNA. This decreases the sensitivity of cancer cells to gemcitabine, providing insight into why K17 expression correlates with shorter patient survival."

According to Dr. Shroyer and his co-authors, the findings define a mitochondrial role for K17 in pyrimidine biosynthesis and uncovers a metabolic vulnerability of K17 basal-like PDAC that they hope can be therapeutically targeted.

This collaborative research involved 25 co-authors from five institutions, including co-senior authors Drs. Natalia Marchenko of the RSOM and Pankaj Singh, Director of the Cancer Center at the University of Oklahoma College of Medicine. Two of the first authors, including Dr. Chun-Hao Pan of Memorial Sloan Kettering Cancer Center, and Lydia (Yinghuan) Liu of Stony Brook University, completed their PhD thesis work in Dr. Shroyer's K17 lab. Dr. Monisankar Ghosh, a third first author also completed his postdoctoral research training in the Department of Pathology at Stony Brook.

The research was supported in part by grants from the National Institutes of Health's National Cancer Institute (NCI), the American Cancer Society and the Pancreatic Cancer Action Network.