Diabetes drugs might someday be leveraged against pancreatic and prostate cancer cells, as a recent PET study from researchers at the University of California, Los Angeles (UCLA), has shed new light on how cancer cells import glucose.
Cancer cells require high amounts of the sugar glucose, and imaging its uptake has provided much information about tumors. The primary method the body delivers glucose to tumors is through passive glucose transporters (GLUTs), but this latest research has demonstrated the importance of another channel of delivery: sodium-dependent glucose transporters (SGLTs).
“The discovery of a new mechanism of glucose transport in cancer raises the question of the relevance of these transporters compared with the already well-known GLUT-dependent glucose uptake,” wrote lead author Ernest Wright, PhD, DSc, professor of physiology in the David Geffen School of Medicine at UCLA, and colleagues. The study was published in the Proceedings of the National Academy of Sciences.
Wright and colleagues first mapped the distribution of SGLTs in human cancer tumors, then measured uptake in fresh tumors using a SGLT-specific radioactive glucose analog, Me4FDG, which is not transported by GLUTs. This revealed that a specific sodium-dependent transporter, SGLT2, was present in pancreatic and prostate andenocarcinomas.
Next, the researchers used mouse cancer models and measured SGLT activity using Me4FDG PET imaging. This confirmed SGLT2 is actively involved in glucose uptake and is vital to growth and survival of the tumors, according to the authors.
The authors noted that while PET imaging of GLUTs is the basis for current methods of diagnosis, this technique is not effective for pancreatic and prostate cancers. “[T]he availability of an SGLT-specific positron-emitting tracer opens very important diagnostic possibilities,” they wrote.
Beyond diagnosis, the results suggest strong therapeutic implications as well. Currently available drugs used to treat diabetes act as SGLT2 inhibitors and thus could one day be used to treat pancreatic and prostate cancers.
“[I]n the case of tumors expressing SGLT2, such as pancreatic and prostate cancers, we predict that the diabetes drugs will reduce glucose uptake, disrupt glycolysis, and reduce tumor growth without significant side effects,” wrote Wright and colleagues.
The team will next turn their attention to a clinical study to investigate the importance of SGLTs in glucose deliver.