Precision dual-targeted vesicles in colorectal cancer
- Reference number
- STP25-0139
- Project leader
- Sjöblom, Tobias
- Start and end dates
- 260601-310531
- Amount granted
- 5 000 000 SEK
- Administrative organization
- Uppsala University
- Research area
- Life Sciences
Summary
Main objectives The overarching objective of this project is to overcome therapy resistance in colorectal cancer (CRC) by integrating tumor-specific drug delivery with precision modulation of tumor drug-metabolizing pathways, thereby restoring sensitivity of resistant CRC to standard therapies while minimizing off-target toxicity. Work plan The project will first use genomic and transcriptomic analyses of CRC to identify and validate key tumor drug-metabolizing targets driving therapeutic resistance. AI-guided protein design will then be applied to engineer bispecific EGFR/B7-H3–targeted extracellular vesicles for precise tumor homing. These EVs will be loaded with siRNAs against validated targets to suppress resistance-associated metabolic pathways, and their therapeutic efficacy and safety will be evaluated in combination with standard CRC drugs in vitro and in vivo. Expected results The project is expected to break the current “therapeutic ceiling” in colorectal cancer by addressing both tumor-specific drug delivery and tumor-intrinsic metabolic resistance. This novel dual-targeted precision strategy is anticipated to enhance clinical responses to standard CRC therapies while minimizing off-target toxicity. Collectively, these advances will establish a new precision-therapy platform with broad potential to overcome treatment resistance across multiple cancer types and generate patentable technologies with strong translational and spin-off potential.
Popular science description
Swedish: Kolorektalcancer är en av de vanligaste och allvarligaste cancersjukdomarna. Patienternas chanser till överlevnad minskar kraftigt om tumören utvecklas så att den slutar svara på behandling. För patienterna innebär behandlingsresistens färre alternativ för fortsatt vård, mer biverkningar och en sämre livskvalitet. Det här projektet sätter patienten i centrum och tar ett nytt grepp om problemet genom att göra cancerbehandlingar både effektivare och skonsammare. Med hjälp av artificiell intelligens utvecklas små biologiska ”transportbärare” som med hög precision kan hitta tumörceller och leverera riktade molekyler som slår ut cancercellernas motståndskraft, samtidigt som frisk vävnad skyddas. Genom att återställa effekten av redan använda standardbehandlingar kan projektet bidra till längre överlevnad, färre biverkningar och en bättre vardag för patienter med kolorektalcancer. På sikt kan samma strategi även komma till nytta för patienter med andra svårbehandlade cancerformer och därmed göra skillnad för många fler. English: Colorectal cancer is one of the most common and deadly forms of cancer, and when tumors become resistant to treatment, patients’ chances of survival drop dramatically. Treatment resistance is therefore one of the most urgent challenges in modern cancer care. This project takes a fundamentally new approach by combining highly precise, tumor-specific drug delivery with innovative strategies that disable cancer cells’ own defense mechanisms. Using artificial intelligence, small biological “delivery vehicles” are developed that can locate tumor cells with high accuracy and deliver targeted molecules that attack resistance from within, while sparing healthy tissue. By restoring the effectiveness of established standard treatments, the project has the potential to significantly improve both survival and quality of life for patients with colorectal cancer. At the same time, the results open the door to rapid clinical application and the development of a new generation of effective and gentle precision therapies—not only for colorectal cancer, but also for other hard-to-treat cancers.