University of Florida College of Pharmacy researchers disclosed that they have discovered a safer and more effective anticancer drug. The new treatment would target leukemia, lymphoma, and breast and lung cancers. Known as DT2216, it affects a protein (called B-cell lymphoma extra-large), which grows malignant cells and strengthens their resistance to treatment. An inhibitor of this protein already exists, but it causes a drop in blood platelets, raising the risk of bleeding. Due to these concerns, the U.S. Food and Drug Administration didn’t approve the drug, and researchers are on the hunt for alternatives.
The New Drug
UF researchers developed the new BCL-XL targeting anticancer drug using a technology that relies on PROTACs, small molecules that rather than merely suppressing cancer-promoting proteins, help cells break them down. Consequently, more potent results ensue against a variety of human tumor cells supported by BCL-XL, yet were less toxic to platelets, unlike previous drugs.
The Preclinical Research
The UF team demonstrated in mathematical and mouse models that DT2216 suppressed growth of several tumors—including T-cell acute lymphoblastic leukemia and drug-resistant breast and small cell lung cancers—on its own and in combination with other drugs, without significantly lowering blood platelet count. The UF team will need to conduct further research before they are able to file an investigatory new drug (IND) application in order to conduct clinical trials on humans.
Daohong Zhou, MD, professor of pharmacodynamics in the UF College of Pharmacy and the Henry E. Innes Professorship of Cancer Research at the UF Health Cancer Center. noted, “We are fascinated by our findings because this was a first-of-its-kind study presenting a novel strategy to reduce the toxicity of an antitumor drug using PROTAC technology.” Dr. Zhou also serves at the UF Cancer Center’s associate director for translation and drug development.
Guangrong Zheng, PhD, associate professor of medicinal chemistry, UF College of Pharmacy, reported, “These findings support the potential of DT2216 to be developed as a first-in-class BCL-XL-targeting antitumor agent.”
Daohong Zhou, MD, professor of pharmacodynamics in the UF College of Pharmacy and the Henry E. Innes Professorship of Cancer Research at the UF Health Cancer Center
Guangrong Zheng, PhD, associate professor of medicinal chemistry, UF College of Pharmacy
The study was supported by a multidisciplinary research team from the University of Florida, the University of Texas M.D. Anderson Cancer Center, Columbia University, Children’s Hospital Los Angeles, and the University of Texas at San Antonio. The team brought together their diverse research expertise in cellular and molecular biology, drug discovery and development, medicinal chemistry, hematology, and bioinformatics.
Call to Action: Interested in learning more about this innovative new early stage drug? Dr. Zhou can be reached at this email.