Abstract

Regimen-related toxicities are common, often painful, disruptive and dose-limiting complications of many forms of chemo- and radiation therapy used for the treatment of cancer. In addition to their symptomatic and physiologic consequences, cancer treatment toxicities significantly increase the use of health resources and the overall cost of care. Despite their frequency and impact on outcome, the overall prevention and management of such side effects is inadequate. The biological basis for toxicities generally is driven by two major factors: indiscriminant clonogenic cell death of dividing normal cells and the activation of a cascade of biological pathways–both culminate in damage, apoptosis and death of the stem cells responsible for the replenishment of normal tissue. The application of nanotechnology to the management of malignancies provides at least three opportunities to minimize toxicities, prevent or treat them and assess their course and severity. Coupling nanodelivery systems to chemotherapy or radiosensitizers could provide an opportunity for more tumor-directed treatment, while simultaneously reducing the risk of collateral damage to non-tumor tissue. Likewise, innovative nano-radiation delivery systems applied to or around tumors might minimize the need for broader radiation fields to achieve comparable levels of tumor kill. Since chemo- or radiation therapy damages epithelial tight junctions, tissue permeability increases providing an opportunity for nano-formulated agents to enhance trans-epithelial drug delivery. Such formulations would result in high local concentrations, but minimize the probability of significant systemic levels. Finally, the application of microfluidic analytics provides a platform for the implementation of biomarkers as practical means to assess the trajectory of many toxicities.

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