Malignant Worms: What Cancer Research Can Learn fromC. elegans

Abstract

Developmental processes in the nematode C. elegans are controlled by pathways of gene functions that are analogous to those used in mammals. Hence, genetic studies in C. elegans have helped build the frameworks for these regulatory pathways. Many homologs of human genes that are targets for mutation in cancer have been found to function at distinct steps within such genetic pathways. This way, studies in C. elegans have provided important clues about the functions of human oncogenes and tumor suppressors. Understanding how human cancer genes function and act in signaling cascades is of great importance. This information reveals what kind of molecular changes contribute to the process of cell transformation. Moreover, additional candidate oncogenes and tumor suppressors may be revealed by identifying the functional partners of genes with an established role in cancer. Furthermore, identifying a cascade of gene functions increases the number of potential targets for therapeutic intervention, as blocking either one of multiple genes may interfere with signal transduction through the pathway. Simultaneous approaches in a number of different model systems act synergistically in solving pathways of gene functions. By using multiple models, the field takes advantage of the strengths of each system and circumvents its limitations. As one of the most powerful genetic animal systems, C. elegans will continue to reveal new mammalian signaling components. In addition, now that the C. elegans genome sequence has been completed, an increasing number of researchers are likely to discover homologs of human disease genes in the nematode and to analyze gene function in the worm model. Combined with the great potential of this animal in drug screens, it is simple to predict that C. elegans will worm its way deeper and deeper into cancer research.

Wormometry‐on‐a‐chip: Innovative technologies for in situ analysis of small multicellular organisms

“…Interestingly, cytometric and photonic technologies have recently begun to find noteworthy applications in analysis of small model organisms (4). Invertebrate (mainly the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster ) and small vertebrate animal models (mainly the clawed African frog Xenopus laevis and zebrafish Danio rerio ) are gaining considerable interest in drug discovery and toxicology (5–10). They offer substantial advantages over cell lines and isolated tissues, providing analysis of cells in the context of cell–cell and cell–extracellular matrix interactions and under normal physiological milieu of the whole organism (8, 11, 12).…”

Invertebrate Models for Biomedical Research, Testing, and Education

“…Because the pathways of gene functions in the two species have many similarities to those in humans, the study of these organisms has provided much insight into tumorigenesis in both humans and animals Schneiderman 1967, 1969;Gilbert 2008;Kirienko et al 2010;Saito and van den Heuvel 2002). Genetics.…”

“…Understanding how multiple genes function together to create a cascade of events provides opportunities for identifying therapeutic agents that can target genes contributing to cancer. C. elegans thus may serve as a key model in screening potential cancer therapeutic agents (Saito and van den Heuvel 2002).…”

How to minimize formation and growth of tumours: Potential benefits of decapod crustaceans for cancer research

“…They were used to identify carcinogenic substances, to analyse the molecular and cellular mechanisms of tumour formation and tumour growth, to identify the genes involved in tumour formation and suppression and to develop drugs for cancer treatment 37, 83, 84. However, in the last 2 decades, non‐mammalian animal models have become increasingly important to investigate particular aspects of carcinogenesis that are currently not well understood, resulting in the development of new concepts and technologies for cancer treatment 34, 36, 85–89…”

“…The fruit fly, Drosophila melanogaster , contributed to investigation of cancer candidate genes, suppressors genes, and the development of cancer treatment by DNA methyltransferase inhibitors 34, 86–88. And the nematode, Caenorhabditis elegans , served as a model to investigate the role that the phylogenetically highly conserved cancer related genes play in normal signalling pathways of developmental processes 89…”