Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma
Menée à l'aide de modèles murins et de xénogreffes dérivées de patients atteints d'un adénocarcinome du poumon de stade précoce, cette étude met en évidence l'intérêt du co-transporteur glucose-sodium de type 2 pour diagnostiquer et traiter la maladie
Like many cancer types, lung cancer is easier to treat when it is detected in its early stages, but this can be difficult to achieve. Scafoglio et al. discovered that a glucose transporter called sodium-glucose transporter 2 is not only expressed in lung cancer but also specifically found in early-stage tumors. Using a radiolabeled tracer specific for this receptor, the authors were able to perform positron emission tomography to identify early tumors that would otherwise remain undetectable. In addition, they found that a class of diabetes drugs called gliflozins, which target the same receptor, is effective at targeting these lung tumors in mouse models.
The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed early in lung tumorigenesis and is found specifically in premalignant lesions and well-differentiated adenocarcinomas. SGLT2 activity could be detected in vivo by positron emission tomography (PET) with the tracer methyl 4-deoxy-4-[18F] fluoro-alpha-d-glucopyranoside (Me4FDG), which specifically detects SGLT activity. Using a combination of immunohistochemistry and Me4FDG PET, we identified high expression and functional activity of SGLT2 in lung premalignancy and early-stage/low-grade LADC. Furthermore, selective targeting of SGLT2 with FDA-approved small-molecule inhibitors, the gliflozins, greatly reduced tumor growth and prolonged survival in autochthonous mouse models and patient-derived xenografts of LADC. Targeting SGLT2 in lung tumors may intercept lung cancer progression at early stages of development by pairing Me4FDG PET imaging with therapy using SGLT2 inhibitors.
Science Translational Medicine , résumé, 2017