Researchers from the University of Florida College of Pharmacy say they have discovered a safer and more effective anticancer drug. The new treatment would target leukemia, lymphoma, and breast and lung cancers.
The drug, known currently as DT2216, affects a protein called B-cell lymphoma-extra large, or BCL-XL, which fuels the growth of malignant cells and strengthens their resistance to therapy. An inhibitor of this protein already exists, but it causes a drop in blood platelets and raises the risk of bleeding, which led the U.S. Food and Drug Administration to deny approval. Since then, scientists have been seeking an alternative.
UF researchers developed the new BCL-XL-targeting anticancer drug using a technology that relies on small molecules that go beyond suppressing cancer-promoting proteins, helping cells break down the proteins. The journal Nature Medicine published their findings on Dec. 2.
The resulting drug works better against a variety of human tumor cells aided by the BCL-XL protein, but were also less toxic to platelets.
“These findings support the potential of DT2216 to be developed as a first-in-class BCL-XL-targeting antitumor agent,” said Guangrong Zheng, Ph.D., an associate professor of medicinal chemistry in the UF College of Pharmacy. Zheng jointly directed the research alongside Daohong Zhou, M.D., a professor of pharmacodynamics in the UF College of Pharmacy.
The researchers have so far demonstrated its effectiveness only in mathematical and mouse models, but say the drug suppressed the growth of several tumors, both on its own and in combination with other drugs. The cancers affected by the drug include T-cell acute lymphoblastic leukemia and drug-resistant breast and small cell lung cancers.
“We were fascinated by our findings because this was a first-of-its-kind study presenting a novel strategy to reduce the toxicity of an anti-tumor drug using PROTAC technology,” said Zhou.
The study was supported by other research teams 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 included researchers with expertise in cellular and molecular biology, drug discovery and development, medicinal chemistry, hematology and bioinformatics.
Additional testing is required before clinical trials can begin with people.
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