Caenorhabditis elegans for research on cancer hallmarks

Abstract

After decades of research, our knowledge of the complexity of cancer mechanisms, elegantly summarized as 'hallmarks of cancer', is expanding, as are the therapeutic opportunities that this knowledge brings. However, cancer still needs intense research to diminish its tremendous impact. In this context, the use of simple model organisms such as Caenorhabditis elegans, in which the genetics of the apoptotic pathway was discovered, can facilitate the investigation of several cancer hallmarks. Amenable for genetic and drug screens, convenient for fast and efficient genome editing, and aligned with the 3Rs ('Replacement, Reduction and Refinement') principles for ethical animal research, C. elegans plays a significant role in unravelling the intricate network of cancer mechanisms and presents a promising option in clinical diagnosis and drug discovery.

Keywords: Caenorhabditis elegans; Cancer; Mutations; Tumors.

Fig. 1.

Hallmarks of cancer that can be investigated in C. elegans. Despite its relative simplicity, C. elegans is amenable to effective modeling of ten of the 14 hallmarks of cancer, leaving just four hallmarks that cannot (yet) be studied in this model.

Fig. 2.

Sustaining proliferative signaling pathways conserved from C. elegans to mammals. Sustained proliferative signaling is one of the original hallmarks of cancer defined in Hanahan (2022), but these pathways have been the subject of intense research, and significant therapeutic success, for far longer. (A,B) A simplified schematic of two well-known proliferative signaling pathways that are often dysregulated in cancer, RTK-RAS/MAPK (A) and PI3K (B), paralleling the analogous mammalian and C. elegans pathways. Sustained signaling through these pathways increases cell proliferation in human cells and causes diverse phenotypes in C. elegans. LET-60/HRAS activation causes a protruding vulva phenotype, whereas sustained AGE-1/PI3K signaling prompts exit from quiescence in some postembryonic cells. P, phosphorylation; PIP, phospholipid; TFs, transcription factors.