A team of researchers has mimicked in Caenorhabditis elegans genetic mutations found in human tumors of the breast, prostate and leukemia. Thus they have identified vulnerabilities that will serve to develop more effective therapies.

At first glance, a worm that measures a millimeter and that must be observed with a magnifying glass does not resemble a human being at all. However, the nematode C. elegans, an animal model used in biomedical research, has approximately the same number of genes that humans have, about 20,000. In addition, most human genes that are related to diseases have a very similar gene, an orthologue, in C. elegans worm.  Thus, for example, the human SF3B1 gene that is mutated in different types of cancer, mainly in leukemia, but also in some breast or prostate tumors, is very similar to the sftb-1 gene of C. elegans.

They are so similar that when the amino acid sequence of the human SF3B1 protein is observed in its regions most affected by cancer mutations, 89% are identical. Precisely some of these amino acids conserved in worms as in to humans are those found mutated in some tumors.

A scientific team from the Bellvitge Biomedical Research Institute (IDIBELL) has taken advantage of these similarities and, through the CRISPR gene editing technique, mimicked the mutations of the SF3B1 gene found in human tumors in  C. elegans . The research work, in which researchers from the Pasteur Institute in Paris have collaborated, has been published in the journal PLoS Genetics.

Target for therapeutic molecules

In this way, possible weaknesses or vulnerabilities of cancer cells that have mutations in SF3B1 have been identified. The authors point to three factors that can function as targets for therapeutic molecules, so that they only kill cancer cells that have the SF3B1 mutation, and no normal cells.

Thanks to CRISPR technology, the functional replacement of C. elegans proteins by their human counterparts will allow these humanized worms to be used to investigate disease mechanisms and predict the involvement of certain mutations in disease development. This system would also serve to find new drugs quickly, efficiently, and ethically.

 

Source: SINC