Pioneering research conducted more than five decades ago paved the way for the idea that certain cancers may be auxotrophic for a particular amino acid, and that amino acid deprivation is one way of treating these tumors. So far, this approach is put in clinical practice by targeting the amino acid asparagine in acute lymphoblastic leukemia, increasing cure from 5 to 95%. However, broadening the application of such an approach to aggressive solid tumors is hampered by the lack of tools for direct measurement of amino acid shortages in cancer cells. Accurate determination of amino acid shortages may offer better diagnosis, stratification of patients, and improved treatment. To sense amino acid shortages in cancer cells we developed a method termed diricore (differential ribosome codon reading). In a paper published in the top journal Nature, we identified using diricore proline deficiency in renal cancer and in breast cancer cell lines propagated in vivo. We also patented the technology for future applications. In a second paper, which is in press in the solid journal EMBOReports, we applied the technology to cells undergoing epithelial to mesenchimal transition, a phenotyype associated with tumor aggressiveness, and identified leucine shortage.
Our results have great future implications and socioeconomic impact as small molecule inhibitors of proline production may be beneficial in fighting cancer, and we have started to screen for them. Also, metabolic changes in aggressive tumours can be exploited for therapy, a theme we are working on with full power.
