UCLA scientists have for the first time identified a new sodium-dependent mechanism to deliver glucose—the body's main fuel that drives tumor growth—to pancreatic and prostate cancer cells, offering new hope in the fight against two of the deadliest forms of the disease.
The study findings further provide the first promising evidence that current sodium-based drug inhibitors and PET imaging techniques could be used to better diagnose and treat these and other forms of the disease, said Dr. Ernest Wright, professor of physiology and lead author of the study.
Cancer cells require high amounts of glucose to grow and survive, and long-standing research has established passive glucose transporters (or GLUTS) as the primary delivery method that our body uses to deliver glucose to tumors. GLUTs serve as the basis for current clinical methods to detect and stage cancer tumors using PET (positron-emission tomography) imaging techniques, but this type of PET imaging does not reliably detect pancreatic and prostate cancers, and its use for diagnosis and staging of these specific diseases is not recommended.
In the two-year study, Wright and co-author Dr. Jorge Barrio, both UCLA Jonsson Comprehensive Cancer Center members, instead focused on two types of sodium-dependent glucose transporters known as SGLT1 and SGLT2. Though widely studied in other diseases, SGLTs have rarely been investigated in relation to these types of cancers. The team specifically sought to investigate their importance in the growth of pancreatic and prostate adenocarcinomas because these SGLTs are found in areas of the body vital to these cancers.
Wright, Barrio and colleagues first mapped the distribution of SGLT1 and SGLT2 in human cancer tumors, then measured glucose uptake in separate tumors using a glucose analog that is transported by GLUTs. They found that SGLT2 does express itself in pancreatic and prostate andenocarcinomas and that it was functional in delivering the glucose that is vital to cancer growth and survival, said Wright.
"This is exciting because it provides strong evidence that SGLT2 inhibitors, such as those currently approved by the FDA to treat diseases like diabetes, could potentially block glucose uptake and reduce tumor growth and survival in pancreatic and prostate cancers," said Wright.
The team further measured SGLT activity in mouse models using a specific radioactive imaging probe for SGLTs, based on PET imaging techniques initially pioneered at UCLA. The results confirmed that SGLT2 as actively involved in glucose uptake into these tumors.
"GLUT imaging probes that have in the past been shown to be of limited effectiveness on these types of tumors," said Barrio, a distinguished professor of molecular and medical pharmacology. "The specific radioactive imaging probe we implemented for SGLTs on these tumors holds tremendous promise to diagnose and stage pancreatic and prostate cancers."
New therapies are urgently needed to fight these diseases. Pancreatic cancer is the fourth-leading cause of cancer-related death in the United States behind only lung, colon and breast cancers, and overall five-year survival rates hover at a devastatingly low 7 percent. Prostate cancer, though generally more treatable and with improved survival rates is still the second-leading cause of cancer-related deaths in men.
Wright and Barrio will next begin a clinical trial to further investigate the importance of SGLTs in glucose delivery. They hope that these findings will lead to the potential use of current Food and Drug Administration-approved SGLT2 inhibitors to reduce the viability of pancreatic and prostate cancer cells in patients.
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