Julia Jakusz, “In Vivo Evaluation of FAN-NM-CH3 and Vitamin C Combination Therapy in Cancer Models”
Mentor: Xiaohua Peng, Chemistry & Biochemistry, Letters & Science (College of)
Poster #12
Breast cancers are highly heterogeneous and aggressive, with limited treatment options and poor prognoses, particularly in triple-negative breast cancer (TNBC), the most aggressive subtype. The Peng group has developed FAN-NM-CH₃, a reactive oxygen species (ROS)-activated prodrug that significantly outperforms FDA-approved alkylating agents like chlorambucil and melphalan. This prodrug selectively responds to H₂O₂, triggering activation and subsequent DNA alkylation, which disrupts cancer cell replication and induces cell death. Given the success of combination therapies in preclinical models, this study evaluates the safety and efficacy of combining FAN-NM-CH₃ with vitamin C in mice. A safety assessment in CD-1 mice determined the maximum tolerated dose, followed by a 10-week efficacy study in MDA-MB-468, MDA-MB-231, and MDA-MB-453 xenograft models. Tumor and body weights were measured weekly. While all treated tumors exhibited shrinkage, complete tumor regression was observed in the MDA-MB-453 model. Notably, monotherapy with either the prodrug or vitamin C showed limited efficacy, whereas the combination therapy demonstrated significant tumor reduction. These findings highlight the potential of FAN-NM-CH₃ in combination therapy, supporting further investigation in patient-derived xenograft (PDX) models to advance clinical translation.