First 'theranostic' agent for treatment of ALL

Study will lead to new approaches in the treatment of pediatric cancers

A team of researchers at Case Western Reserve University School of Medicine has developed the first "theranostic" agent for the treatment of acute lymphoblastic leukemia (ALL). ALL is the most common type of childhood cancer diagnosed in approximately 5,000 new cases each year in the United States. The findings provide insight into pediatric oncology that specifically focuses on the development of "theranostic" agents-- a treatment platform that combines a selective diagnostic test with targeted therapy based on the test results.

Discovery of this new class of drugs is the first step towards new diagnostic markers and therapeutic approaches in treatments with anti-cancer agents of numerous other cancers in addition to ALL.

"This discovery takes a chemical biology approach to target ALL. Our nucleosides represent a new class of theranostic agents that provide an original approach to achieving personalized treatments against pediatric leukemia," says Anthony J. Berdis, PhD, assistant professor of pharmacology at Case Western Reserve School of Medicine.

"We've developed a non-natural nucleoside that specifically targets this form of childhood leukemia. The combination of therapeutic and diagnostic activities will provide more selective and more expedient ways to treat patients by optimizing the dosages needed to kill the cancer cells without affecting normal cells. This selectivity should minimize the development of adverse side effects typically associated with conventional anti-cancer nucleosides," says Dr. Berdis.

Using an enzyme implicated in the disease, terminal deoxynucleotidyl transferase (TdT) which serves as a biomarker and is overexpressed in 90 percent of ALL patients, Dr. Berdis and his team designed a new selective anti-cancer agent against ALL. By evaluating the anti-leukemia activities of two non-natural nucleotides designated 5-NITP and 3-Eth-5-NITP, the investigators strategically placed novel functional groups on these agents so that they could be tagged with fluorogenic dyes. These taggable nucleotides improve the accuracy of dosing regiments and could accelerate clinical decisions regarding therapeutic intervention. The next steps will be validation in animal studies and toxicology testing, leading to clinical trials.