Tumor Models Incorporating Aspects of Tumor Microenvironment for Novel Cancer Nanotherapies

Several studies, including our own, have demonstrated that genetic alterations of tumor cells are not the sole driving force behind tumor development and that tumor growth, metastasis and response to treatment are intimately controlled by the tumor microenvironment. An appropriate representation of the tumor microenvironment in tumor models can thus have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. This presentation will demonstrate a multimodal nanotherapeutic system that functions via the biological response to radiation in the tumor endothelial cells using an in vitro/ in vivo tumor model incorporating characteristics of tumor microenvironment. This presentation will also elucidate upon the utility of 3D tumor models in vitro to understand the sustained release of active drug from liposomal formulations at the tumor site over a prolonged period of time, simulating the action of localized metronomic therapy in cancer, a treatment modality that targets the tumor microenvironment. Such tumor models that lend themselves to controlled experimental manipulation in a cost-effective and reproducible manner are expected to better predict treatment response and accelerate drug development.

References:

1. Sethi P, Jyoti A, Swindell E, Langner UW, Feddock JM, Nagarajan R, O’Halloran TV and Upreti M. 3D Tumor Tissue Analogs and their Orthotopic implants for Understanding Tumor-targeting of Microenvironment-responsive Nanosized Chemotherapy and Radiation. Accepted for publication in Nanomedicine: Nanotechnology, Biology & Medicine.
2. Jyoti A, Fugit K, Sethi P, McGarry RC, Anderson BD and Upreti M. An in vitro assessment of liposomal topotecan simulating metronomic chemotherapy in combination with radiation in tumor-endothelial spheroids. Resubmitted wiht minor edits to Scientific Reports.