Research Project
10260497
The objective of this study is to develop and validate clinically translatable mechanical interventions that can be used to enhance drug delivery to cancerous bone tumors. In preliminary work, the City College of New York (CCNY) and Memorial Sloan Kettering Cancer Center (MSKCC) investigative team has demonstrated that delivery of an intravenous drug can be significantly enhanced in mechanically loaded tumor-bearing rat tibiae. Based on the promising preliminary results, this study will collect important pre-clinical data that will test two different mechanical interventions in a rat model and then translate the results to develop a clinical protocol to enhance drug delivery to bone tumors. Two different approaches of applying mechanical intervention will be used to enhance tumor drug delivery in a rat model of metastatic bone cancer to assess their potential applicability to human patients. Specific Aim 1 will simulate how exercise would be used in the clinic to enhance drug delivery to bone tumors. Specific Aim 2 will utilize very low-magnitude mechanical vibration that could also be delivered easily in a clinical setting. Specific Aim 3 will build upon the findings from the pre- clinical rat studies to design a clinical IRB protocol that would target patients most likely to benefit from mechanical intervention during cancer drug administration. The long-term goal of this work is to establish a clinical treatment that uses load-bearing exercise or low-intensity vibration to enhance tumor delivery of therapeutic drugs. This low-risk and easy-to-implement approach may enhance a drug's uptake and therapeutic effect in the most clinically relevant skeletal areas while potentially decreasing systemic drug dosage and unwanted side effects.
