ABSTRACT
Xenopus has made many seminal contributions to numerous research fields and has been especially critical for deciphering early vertebrate development. With the emergence of zinc finger nucleases (ZFNs), TALENs, and CRISPR/Cas9 techniques, Xenopus is receiving increased attention with regard to modeling of human diseases, including cancer. X. tropicalis is especially uniquely placed for these applications because it combines the general amphibian features of large externally developing embryos, which are straightforward to inject with genome editing reagents, with a relatively short life cycle and a true diploid genome. The generation of cancer-prone lines carrying a heterozygous mutant tumor suppressor gene (TSG) allows the modeling of hereditary cancer-predisposition syndromes. Alternatively, injection of multiplexed genome editing reagents and rapid F0 screening of such mosaic mutant animals allows the experimental investigation of cooperative tumor suppressive activity of multiple genes in specific cancer contexts, thereby allowing the identification or confirmation of novel driver gene mutations. Furthermore, via the generation of mosaic mutant X. tropicalis tumor models, it is possible to design strategies to identify cancer dependencies built on principles of cell-specific clonal selection. In addition, possibilities for in vivo compound treatments are highlighted. Finally, this chapter provides perspectives for novel tools that will facilitate future in vivo monitoring of tumor progression as well as precise genome editing techniques that can be useful for generating genetically engineered Xenopus models (GEXMs) even more closely mimicking the patient situation.
