Hidden backup route for cysteine production may aid cancer resistance
Researchers found that mammalian cells can produce the amino acid cysteine even when the known disulfide reductase systems are disabled, a survival mechanism previously thought impossible. This backup pathway may help cancer cells withstand treatment, so disabling it could make tumors more vulnerable. The discovery was published in Nature Chemical Biology.
The discovery emerged from a 2014 observation when genetically engineered mice survived despite lacking functional disulfide reductase systems, contradicting established scientific assumptions. Schmidt had previously created mouse lines with liver cells missing one of the two main reductases, and their physiological responses prompted him to question the prevailing belief that such survival was impossible.
The backup mechanism remained unexplained for seven years until collaboration with Peter Nagy's team in Budapest provided analytical tools to trace how cells obtained cysteine from cystine without the standard systems. The finding suggests cancer cells may exploit this pathway to resist treatment, making it a potential therapeutic target.
This discovery could reshape cancer treatment strategies by identifying a vulnerability in tumor cells. If the backup cysteine pathway can be selectively disabled, cancer cells might become more susceptible to existing therapies, while healthy cells could potentially be protected. The research may also influence understanding of metabolic diseases and conditions involving oxidative stress. However, translating these findings into clinical applications will require substantial further investigation, and any therapeutic approach would need careful validation to ensure safety and efficacy.