Designed protein binders to conserved MYC regions reach low-nanomolar affinity, reduce MYC-MAX proximity in cells, and are depleted from MYC-dependent cancer cells in culture and mouse pancreatic tumors.

bioRxiv · Oct 22, 2026 · PreprintBiochemistry✦ In-depth digest

A window trial in metastatic pancreatic ductal adenocarcinoma reveals resistance mechanisms to targeting the KRAS-MEK pathway

Motoyuki Tsuda, Dove J. Keith, Colin J. Daniel, Carl Pelz, Katie E. Blise, Tugba Y. Ozmen, Furkan Ozmen, Kevin Hawthone, Jennifer R. Eng, Xi Li, Xiaoyan Wang, Hayley Zimny, Shamilene Sivagnanam, Konjit Betre, Nell C. Kirchberger, , Rosalie C. Sears

The paper identifies resistance mechanisms to KRAS-MEK pathway targeting in PDAC by analyzing clinical trial data and multi-omics profiles, showing that KRAS/MYC co-gain correlates with resistance and that co-targeting these genes is synergistic.

bioRxiv · Dec 15, 2025 · PreprintCancer Biology

Myc and Kras cooperate in adult acinar cells to drive phenotypic heterogeneity, metastasis, and therapeutic resistance in a novel pancreatic cancer mouse model

Isabel A. English, Patrick Joseph Worth, Kevin Hawthorne, Macarena Vergara, Katherine R. Pelz, Ashley L. Kiemen, Vidhi Shah, Katie E. Blise, Carl Pelz, Motoyuki Tsuda, Michael B. Heskett, Amy T. Farrell, Brittany L. Allen-Petersen, Phillip Jimenez, Meghan M. Joly, , Rosalie C. Sears

This study develops a novel pancreatic cancer mouse model by expressing Myc and mutant Kras in adult acinar cells, showing metastasis and therapeutic resistance similar to human PDAc.

bioRxiv · Jul 14, 2025 · PreprintCancer Biology

PIN1 Drives Cellular Plasticity and Immune Modulation in Chronic Pancreatitis

Vidhi M. Shah, Alexandra Q. Bartlett, Canping Chen, Aubry Matter, Alexander Smith, Hayley Zimny, Xiaoyan Wang, Colin J. Daniel, Jenny Eng, Syber Haverlack, Isaac Youm, Motoyuki Tsuda, Nicholas L. Calistri, Matthew Reyer, Terry K. Morgan, , Rosalie C. Sears

This study shows PIN1 promotes cellular plasticity and immune changes in chronic pancreatitis, with genetic or pharmacological inhibition reducing disease severity.

bioRxiv · May 13, 2025 · PreprintCell Biology