Research Update
Glioblastoma: Evaluating Multiple Drug Candidates at One Time
Dr. Andrew B. Lassman
Columbia University Irving Medical Center is among the first to enroll patients with glioblastoma in a new type of clinical trial that plans to speed the identification and development of the most promising therapies for the disease. Instead of evaluating each therapy in its own separate clinical trial, GBM AGILE (Adaptive Global Innovative Learning Environment) is designed to evaluate several drug candidates at once by studying multiple treatment groups concurrently without the need for separate protocols. “There’s really no limit to the number of therapies that can be tested with this design for first-line and recurrent disease,” says Andrew B. Lassman, MD, Chief of Neuro-Oncology at NewYork-Presbyterian/Columbia, and a GBM AGILE global study chair and member of the arm selection committee.
Because all treatments are compared to one common control group, patients are more likely to get an experimental therapy. Tumor tissue from participants will undergo analyses to identify biomarkers that may be associated with a patient’s response. As the trial accumulates data, its algorithm refines the randomization process, so that patients have a better chance of getting a treatment that appears to show benefit. This also allows investigators to quickly identify treatments that are more encouraging than the standard of care, while less promising therapies can be dropped. “This trial design offers a way to lower the cost, time, and number of patients needed to test new therapies for newly diagnosed or recurrent glioblastoma,” says Dr. Lassman.
Colon Cancer: High-Fructose Corn Syrup Fuels Tumor Growth
Dr. Lewis C. Cantley
Dr. Marcus D. Goncalves
In a study published in the March 22, 2019 issue of Science, researchers at Weill Cornell Medicine showed how high-fructose corn syrup fuels the growth of colon tumors in mice and demonstrated a potential strategy to block this excess tumor growth. “The study shows that colorectal polyps feed on high-fructose corn syrup and explains the molecular mechanism by which this drives the growth of the tumor,” says Lewis C. Cantley, PhD, Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and co-senior author.
“When you give the mice this additional sugar the tumors grow much bigger,” says lead author Marcus D. Goncalves, MD, PhD, an endocrinologist at NewYork-Presbyterian/Weill Cornell Medical Center. “If you are predisposed to getting polyps, you should not be drinking any sugar-sweetened beverages.”
When mice are fed high-fructose corn syrup, the sweetener delivers an excess of both glucose and fructose to the colon. The researchers showed colon tumors readily take in both sugars. The enzyme ketohexokinase (KHK) changes the fructose into fructose-1-phosphate, which was found to promote the tumor's ability to use glucose for energy and generate the fats necessary for tumors to grow. “We expect that consuming beverages or processed foods with added sucrose is likely to have the same effect as consuming drinks with high-fructose corn syrup, since sucrose has a similar composition,” says Dr. Cantley. “Our study showed two genetic ways to reverse the high-fructose corn syrup’s effects by targeting KHK and an enzyme necessary for fat production.”