Research ArticleCancer

Sodium-glucose transporter 2 is a diagnostic and therapeutic target for early-stage lung adenocarcinoma

See allHide authors and affiliations

Science Translational Medicine  14 Nov 2018:
Vol. 10, Issue 467, eaat5933
DOI: 10.1126/scitranslmed.aat5933

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Lung cancer search and destroy

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.

Abstract

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.

View Full Text