This project aims to further exploit a fast, semi-high throughput and cheap animal model for identifying and/or characterizing promising drug targets for treating desmoid tumors. In addition the platform allows pre-clinical assessment of novel candidate therapeutic compounds. The project builds on a recently developed genetic desmoid tumor model in the frog Xenopus tropicalis, This model, which induces mosaic loss-of-function mutation in the tumor suppressor gene apc,  presents a unique and novel experimental platform that (i) allows the rapid screening and evaluation of genes that contribute to the growth of the tumor, (ii) can serve to assess the clinical relevance of novel drug targets for treating desmoid tumors and (iii) can be used as a preclinical drug screening/assessment. A new methodology was developed called CRISPR/Cas9-mediated Selection Identification of genetic Dependencies (CRISPR-SID) that allows in vivo elucidation of cancer cell vulnerabilities in genetic cancer models. The methodology hinges on the fact that for a genetic dependency there is an incapability for recovering tumors carrying biallelic frameshift mutations in this gene. We will now further expand our model by the inducing activating point mutations in the ctnnb1 gene using Cas9 Base Editors. In addition we want to use the model for validating novel dependency factors coming out of an in vitro screen and to further investigate the role of the transcription factor CREB3L1 and its link to collagen synthesis and secretion in the process of desmoid tumor formation.