Engineered human serine dehydratase enzymes are designed to efficiently degrade serine, an amino acid crucial to cancer cell metabolism, and inhibit cancer growth. These enzymes, with improved stability, activity, and bioavailability, offer a targeted cancer treatment option with fewer adverse effects.
Traditional chemotherapeutic agents often lack specificity, leading to severe side effects due to their impact on healthy cells. The field of cancer metabolism has gained significant attention due to its potential for developing targeted therapies. Cancer cells often exhibit altered metabolic pathways to support their rapid proliferation and survival.
One such adaptation is the increased reliance on certain amino acids, such as serine, which is critical for various biosynthetic processes. Serine plays a vital role in nucleotide synthesis, antioxidant production, and other cellular functions that are essential for tumor growth. As a result, targeting amino acid metabolism has emerged as a promising strategy to selectively inhibit cancer cell growth while minimizing damage to normal cells. This approach aims to exploit the metabolic vulnerabilities of cancer cells, offering a more precise and potentially less toxic alternative to conventional chemotherapy.
Current methods to target amino acid metabolism in cancer therapy face several challenges. Small-molecule inhibitors targeting amino acid biosynthesis pathways have been developed, but many cancers can circumvent these interventions by upregulating synthetic pathways or increasing amino acid uptake from the environment. Moreover, while dietary restriction of serine has shown some efficacy in reducing tumor growth despite only modestly lowering serine blood levels, it is not a practical long-term solution due to issues with patient compliance and the body's ability to compensate for dietary deficiencies. These limitations highlight the need for more effective, targeted approaches to disrupt amino acid metabolism in cancer cells, which could potentially improve treatment outcomes and reduce adverse effects.
The technology involves engineered human serine dehydratase enzymes that have been modified to enhance their ability to degrade serine, an amino acid crucial for cancer cell metabolism. These enzymes have specific amino acid substitutions that increase their catalytic efficiency compared to the native enzyme. The modifications allow robust depletion of serine levels in the bloodstream, thereby inhibiting cancer cell proliferation. The engineered enzymes can be coupled with polyethylene glycol (PEG) to extend bioavailability. The technology also includes nucleic acids encoding these enzymes, expression vectors, host cells for production, and pharmaceutical formulations for therapeutic use in cancer treatment. This approach targets cancer cells with high serine dependency, potentially offering a more selective and less toxic treatment option compared to conventional therapies.
This technology is differentiated by its focus on targeting the metabolic dependencies of cancer cells, specifically their reliance on serine. Unlike traditional therapies that often lack tumor specificity and result in severe toxicities, this approach leverages the unique metabolic requirements of cancer cells to achieve selective inhibition. The engineered enzymes are derived from human sequences, minimizing the risk of immunogenic reactions that can arise from non-human proteins. Additionally, the use of PEGylation enhances the enzymes' stability and circulation time in the body, further improving their therapeutic potential. By depleting essential amino acids systemically, this technology provides a novel method for cancer treatment that can be finely controlled and adjusted to patient needs, offering a promising alternative to existing cancer therapies.