Caenorhabditis elegans: A Versatile In vivo Model for Decoding Conserved Oncogenic Signaling Pathways

Caenorhabditis elegans (C. elegans) is a genetically tractable, transparent, and cost-effective metazoan model that bridges conventional cell-culture assays and mammalian systems for mechanistic cancer research. This pathway-focused review covers representative studies of conserved RAS/MAPK, Notch, and Wnt signaling and is organized around pathway conservation, mutant strains, quantitative phenotypes, genetic tools, and applications in mechanism studies, compound screening, and chemosensation-based assays. We first describe the conservation of pathway components and tumor-relevant phenotypes, including germline overproliferation and the multivulva (Muv) phenotype. We then catalog representative mutants, such as gain-of-function glp-1 and let-60 strains and loss-of-function gld-1 and lip-1 models, that enable analysis of stem-cell maintenance, ectopic proliferation, and signaling dysregulation. In addition, we discuss available tools for model construction, including RNA interference, transgenesis, MosTIC, TALENs, and CRISPR/Cas9, highlighting their strengths and limitations for cancer-related gene-function studies. Finally, we summarize published applications of C. elegans in anticancer drug screening, pathway discovery, and tumor-associated chemosensation. By integrating genetic conservation with scalable in vivo phenotyping, C. elegans provides a complementary platform for hypothesis generation, pathway validation, and early-stage therapeutic discovery, while its limitations in adaptive immunity and organ complexity should be recognized when translating findings to human cancer biology.