Abstract 947: A nanodroplet cell processing platform for identifying synergistic drug combinations for neuroblastoma treatment in TH-MYCN transgenic mice

Abstract Neuroblastoma is the most common pediatric extracranial solid tumor and contributes to more than 15% of child mortality. It is characterized by extreme heterogeneity and high-risk tumors often resulting in poor prognosis. Currently, chemotherapy is a prevailing standard treatment for neuroblastoma. However, it is plagued by multiple challenges such as drug resistance and debilitating side effects. Synergistic drug combination is proposed as an innovative approach to potentially improve clinical outcomes of single-agent chemotherapy. We propose a novel approach to screen for effective chemo-synergistic drug combinations using Bioinspired nanodroplet processing (BioNDP) screening platform. This platform overcomes the limitations of conventional drug screening approaches, including the requirement for large cell numbers and the low translation rate from bench to bedside. In this study, we utilize TH-MYCN transgenic mice, a well-known genetically engineered mouse model of neuroblastoma that recapitulates critical genetic and clinical aspects of high-risk MYCN-amplified neuroblastoma. With its genetically homogeneous background and spontaneous tumor development, TH-MYCN mice offer a valuable comparison to traditional xenograft mouse models. We have also developed an optimal procedure of primary murine tumor isolation using both negative and positive selection approaches. The purity of the isolated cells was verified with GD2 expression, one of well-known marker of neuroblastoma. In addition, we have successfully identified an effective drug combination of cyclophosphamide, doxorubicin, and vincristine, using primary neuroblastoma tumor samples derived from TH-MYCN transgenic mice as a target. The in vitro synergistic effect of primary mouse tumor cell cytotoxicity was confirmed by using luminescent cell viability assay. Further in vivo experiments have demonstrated the therapeutic efficacy of this selected drug combination in suppressing tumor growth and improving survival rate in all TH-MYCN transgenic mice treated. To sum up, we aim to establish a future patient-centric paradigm by which minimal primary cell samples from a personalized biopsy of patients may undergo drug screening, leading to the identification of a tailored drug combination. The BioNDP platform we developed may become a pivotal resource for personalized therapy to ensure a faster and more efficient treatment strategy for patients. Citation Format: Yen-Tzu Liao, Zhi-Kai Yu, Ching-Te Kuo, Wen-Ming Hsu, Yi-Xun Huang, Hsinyu Lee. A nanodroplet cell processing platform for identifying synergistic drug combinations for neuroblastoma treatment in TH-MYCN transgenic mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 947.