Study Identifies Mechanism Fueling Growth of Pancreatic and Prostate Cancer Cells
UCLA Jonsson Cancer Center scientists have identified a new mechanism that delivers a key substance that fuels the growth of pancreatic and prostate cancer cells, a finding that offers new hope in the fight against two of the deadliest forms of the disease. Their findings were published by Scafoglio et al in PNAS.
Cancer cells require high amounts of glucose to survive and grow, and long-standing research has established passive glucose transporters, known as GLUTS, as the primary method the body uses to deliver glucose to tumors. But the results of a 3-year study by UCLA researchers demonstrated that pancreatic and prostate cancer cells also utilize glucose from sodium-dependent glucose transporters known as SGLTs—specifically SGLT2.
The findings provide the first promising evidence that positron-emission tomography (PET) imaging techniques and SGLT2 inhibitors could be used to better diagnose and treat pancreatic and prostate cancers, said Ernest Wright, PhD, DSc, Professor of Physiology in the David Geffen School of Medicine at UCLA.
“This is exciting because it provides strong evidence that SGLT2 inhibitors, such as those currently approved by the FDA to treat diabetes, could potentially block glucose uptake and reduce tumor growth, increasing survival in pancreatic and prostate cancers,” said Dr. Wright.
Study Details
Researchers first mapped the distribution of SGLTs in human cancer tumors and then measured glucose uptake in fresh tumors using a glucose analog specifically transported by SGLTs. They observed that SGLT2 was present in pancreatic and prostate andenocarcinomas and that it assisted in delivering the glucose vital to cancer growth and survival, Dr. Wright said.
The team then measured SGLT activity in a mouse cancer model using a radioactive imaging probe for SGLTs. This measuring procedure is based on PET imaging techniques pioneered at UCLA. The results confirmed that SGLT2 is actively involved in glucose uptake and growth of these tumors.
Passive glucose transporters serve as the basis for current clinical methods to detect and stage cancer tumors using PET imaging techniques, but this type of imaging is not effective for pancreatic and prostate cancers, said Jorge Barrio, PhD, a Distinguished Professor of Molecular and Medical Pharmacology at UCLA.
“The specific radioactive imaging probe we have developed for SGLTs on these tumors holds tremendous promise to diagnose, stage, and monitor SGLT-based therapeutic interventions in pancreatic and prostate cancers and potentially other cancers,” said Dr. Barrio.
Drs. Wright and Barrio will next begin a clinical study to further investigate the importance of SGLTs in glucose delivery. They hope that these findings will lead to the potential use of current U.S. Food and Drug Administration–approved SGLT2 inhibitors to reduce the viability of pancreatic and prostate cancer cells and increase patient survival.
Drs. Barrio and Wright are the corresponding authors of the PNAS article.
The research was supported in part by funding from the UCLA Jonsson Comprehensive Cancer Center Impact Grant program and from the National Institutes of Health.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
