Researchers have developed a treatment platform that combines a selective diagnostic test with targeted therapy, based on the results of the test, for youths with acute lymphoblastic leukemia (ALL), the most common type of childhood cancer.
This “theranostic” strategy employs two new nonnatural nucleotides, developed by a team at Case Western Reserve University School of Medicine in Cleveland, Ohio. The new selective anticancer agents, which specifically target ALL, were designed by Anthony J. Berdis, PhD, assistant professor of pharmacology at the medical school, and colleagues.
Working from the knowledge that the enzyme TdT (terminal deoxynucleotidyl transferase) is overexpressed in approximately 90% of ALL patients and is an excellent biomarker of poor prognosis, Berdis and coinvestigators used the enzyme to create two nonnatural nucleotides, designated 5-NITP and 3-Eth-5-NITP, to work against leukemia cells that overexpress TDT. The researchers then placed novel functional groups on these agents so that the agents could be tagged with fluorogenic dyes.
The tagged nucleotides improved the accuracy of dosing regimens and could help accelerate clinical decisions regarding therapeutic interventions, explained Berdis and associates in their report in ACS Chemical Biology. The next steps will be to validate these results in animal studies and toxicology testing, leading to clinical trials.