Karuna Ganesh, Physician Scientist at Memorial Sloan Kettering, shared a post on X:
“We are thrilled to share our latest work out today Developmental Cell! Appendiceal adenocarcinoma (AC) is a rare, aggressive cancer that frequently spreads to the peritoneum. Until now, lack of robust preclinical models has severely limited drug discovery.
We established a first-in-class stable biobank of 16 long-term cultured AC patient-derived organoids (PDOs). Crucially, this biobank includes matched pairs of simultaneously resected primary AC and peritoneal carcinomatosis (AC-PC) from the same patients.
Using these paired models, we developed an organoid orthotopic intraperitoneal xenograft model that recapitulates human diffuse peritoneal carcinomatosis. PC organoids retain a higher metastatic capacity and decreased growth factor dependency compared to the primary tumors.
What drives this aggressive peritoneal spread? Single-cell profiling of the primary-met pairs revealed striking cellular plasticity. We observed a clear dedifferentiation from mucinous states in the primary tumors into intestinal stem cell and fetal progenitor states in mets.
Massive congratulations to Ahmed Mahmoud, our first PhD graduate, Karuna Ganesh Lab, HHMI NEWS, Gilliam Fellow, Weill Cornell, and surgeon-scientist Georgios Karagkounnis for driving this incredible effort!
A huge thank you to our patients, patient advocates, and our collaborative team at Memorial Sloan Kettering Cancer Center, and rare cancer funding from Dalton Family Foundation and Cycle for Survival. We hope these new models will finally open the door to precision therapies for appendiceal cancer.
Here’s the Research Highlight by the amazing Ian Demsky”
Title: An appendiceal cancer organoid biobank identifies phenotypic evolution and druggable dependencies of peritoneal carcinomatosis
Authors: Ahmed Mahmoud, Christine Sukhwa, Michael Giarrizzo, Philip H. Choi, Jura Pintar, Henry Walch, Nan Zhao, Jonathan Bermeo, Sebastian Chung, Manisha Raghavan, Samhita Bapat, Qingwen Jiang, Julia Meredith, Canan Firat, Andrea Cercek, Michael B. Foote, Nikolaus Schultz, Walid K. Chatila, Garrett M. Nash, Jinru Shia, Francisco Sanchez-Vega, Steven Larson, Arvin C. Dar, Neal Rosen, Georgios Karagkounis, Karuna Ganesh
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