Rapamycin Shows Promise in Treating APC-Mutant Colon Cancer Precursors
By Aline Habib, Rose Mamistvalov, and Prof. Dalit Ben-Yosef
Published in Cancer Gene Therapy, July 2025
In a groundbreaking study, Aline Habib, Rose Mamistvalov, and principal investigator Prof. Dalit Ben-Yosef from Tel Aviv Sourasky Medical Center and Tel Aviv University have demonstrated that rapamycin, a known mTOR inhibitor, can restore normal differentiation in colon organoids derived from human embryonic stem cells (hESCs) carrying specific APC gene mutations.
The team used hESC-derived colon organoids from patients with familial adenomatous polyposis (FAP), a hereditary condition leading to colorectal cancer. In cells with a truncating APC mutation (FAP1), mTOR signaling was abnormally high, suppressing normal colon development. Treatment with rapamycin successfully reversed these defects, restoring the formation of mature, complex organoids. This effect was not seen in organoids with a different APC mutation (FAP2) that did not exhibit mTOR pathway activation.
Importantly, the researchers validated these findings using colon biopsies from the same FAP1 patient who donated embryos for the stem cell lines. These tissues also showed strong mTOR pathway activity, supporting the model’s translational relevance.
The study highlights rapamycin’s potential as a personalized therapy for a subset of FAP patients and emphasizes the value of stem cell–based organoid models in cancer research.
Read the full article: https://www.nature.com/articles/s41417-025-00935-3 [1]