Rutgers Biomedical and Health Sciences has received a USD 1.78 million National Cancer Institute R01 award to identify biomarkers and evaluate therapeutic strategies for chemotherapy-induced cognitive impairment (CICI) in pediatric cancer survivors, a condition affecting an estimated 35% of childhood cancer survivors in the US.
The grant, running through May 2029, targets a clinically underserved consequence of otherwise successful cancer treatment. As pediatric acute lymphoblastic leukemia (ALL) survival rates have improved substantially, long-term neurocognitive deficits — colloquially termed "chemobrain" — have emerged as a significant quality-of-life burden. The research centers on PARP1, an enzyme activated by DNA damage that depletes cellular NAD+, a metabolite increasingly linked to neurodegeneration. Preliminary data from the team indicated that methotrexate, cisplatin, and paclitaxel each induce neuronal DNA damage and elevated cleaved PARP1 expression in mouse hippocampus and human excitatory neurons. Notably, the FDA-approved PARP1/2 inhibitor veliparib demonstrated prevention of cisplatin-induced anxiety-like behavior and neurogenic defects in preclinical models.
The study will assess veliparib's neuroprotective effects in juvenile mouse models of T-cell ALL, including patient-derived xenograft models, while also evaluating whether the drug compromises antineoplastic efficacy — a critical safety question for any combination strategy in active cancer treatment. A pediatric ALL patient cohort will be used to validate NAD+ metabolites as candidate blood or cerebrospinal fluid biomarkers for predicting cognitive vulnerability.
Principal investigators Mi-Hyeon Jang and Peter D. Cole lead the work. The grant is administered through Rutgers' neurosurgery department, reflecting the translational neuroscience framing of the project.