Drugs currently used to treat diabetes could also be effective against some types of cancer by preventing the delivery of glucose to those cells and reducing tumor growth, according to new research published in the journal Proceedings of the National Academy of Sciences.
In the study, scientists at UCLA’s Jonsson Comprehensive Cancer Center explained how they were able to identify a new mechanism that delivers sugars that fuel the growth of prostate and pancreatic cancer cells, and which provides a potential new way to treat these diseases.
Researchers have long known that cancer cells require glucose to survive and grow, but in this latest study, the UCLA researchers identified a new method used to transport sugar molecules to tumors, as well as a new medication that could cut off this newly discovered supply line.
The three-year study found that pancreatic and prostate cancer cells can utilize glucose from sodium-dependent glucose transporters (SGLTs), and that positron emission tomography (PET) imaging techniques and SGLT2 inhibitors could be used to help doctors better diagnose and treat these life-threatening conditions, the study authors said in a statement.
So how did this discovery come about?
Dr. Ernest Wright, a member of the Jonsson Comprehensive Cancer Center and a professor of physiology at the UCLA David Geffen School of Medicine who co-led the research along with his colleagues Drs. Jorge Barrio and Claudio Scafoglio, explained to redOrbit that the team was imaging cancer patients with a new glucose probe for SGLTs using PET.
While doing, they found that some cancers, including prostate and glioblastomas, accumulated this new tracer, methyl-4-deoxy-4-[F-18]fluoro-D-glucopyranoside. The tracer is only imported into cells by SGLTs, Dr. Wright said, while the glucose tracer used in clinical PET, 2-deoxy-2[F-18]fluoro-D-glucose, is only accumulated by passive glucose transporters (GLUTS).
These observations, coupled with the introduction of FDA-approved drugs to block glucose reabsorption in the kidney by SGLT2 as part of the treatment of diabetes, allowed them to test whether or not these drugs acting on SGLT2 could block glucose import into tumors.
“Our study shows that 1. SGLT2 is responsible for glucose import into pancreatic and prostate tumors excised from patients; 2. PET imaging using the new SGLT tracer reduced glucose uptake into pancreatic and prostate tumors grown in mice; and 3. treatment of mice with the new diabetes drugs reduced tumor growth,” Dr. Wright told redOrbit via email.
Next steps involve UCLA-approved human trials
He and his fellow researchers now plan to conduct PET studies on cancer patients as part of a UCLA-approved human research protocol, with the goal of demonstrating that a single oral dose of a new diabetic drug could effectively reduce glucose update into their tumors.
Two one-hour PET scans will be carried out on each patient during the course of the study, Dr. Wright said. One will be a control scan, while the other will be taken after the dose of a US Food and Drug Administration (FDA) approved SGLT2 inhibitor is administered to the patient. They hope that this treatment will reduce cancer cell viability and increase patient survival.
“If such studies show that the SGLT2 reduced glucose uptake into tumors clinical trials will then be conducted to determine if treatment with the SGLT2 drugs, alone or in combination with current therapies reduce tumor growth,” Dr. Wright said. “Given that the SGLT2 inhibitors have undergone extensive trials on tens of thousands of diabetic patients with few notable side effects, extensive safely trials with cancer patients may not be required.”
He added that while the focus of these particular initial studies was on pancreatic cancer, given their high incidence and very low five-year survival rates, his team typically carries out “very basic research on the human biology of SGLTs that is not targeted to any specific disease… we move rapidly to translate our findings to major clinical problems such as diabetes and cancer.”
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