Crook is supported by the Chief Scientific Officer of Scotland, The Leng Foundation, and The Anonymous Trust.
Malignant gliomas are among the most pernicious of human tumors and are characterized as regionally invasive, usually recurring within two centimeters of their origin after resection [1]. Although many advances in treatment have been made, they have yielded only modest survival

benefits [2]. Numerous Inhibitors,research,lifescience,medical chemotherapeutic drugs have demonstrated significant antitumor activity in preclinical studies, but often this effectiveness is not translated into clinical trials in humans. A major factor contributing to this is the limitation of systemic delivery, namely, the impermeability of the blood-brain barrier as well as dose-limiting toxicities of many compounds. This highlights the need for efficient, specific methods of delivery in the treatment of human GBM. The ideal delivery method would be one that achieves adequate Inhibitors,research,lifescience,medical coverage of the tumor volume while minimizing any unwanted toxicities. Optimal delivery requires three important components: the ability to target Inhibitors,research,lifescience,medical the tumor while minimizing local

and systemic effects, applicability over a wide range of therapies, and a safe, efficacious method of continuous delivery with noninvasive methods to monitor volumes of distribution (Vd) of agents. In this paper, we describe our experience with convection-enhanced delivery (CED) Inhibitors,research,lifescience,medical across these three domains and highlight the translational goals of this work. The ultimate goal is to safely bring such systems and therapies to human trials, and eventually, to optimize these methods in clinical practice and establish standards of care. 2. Convection-Enhanced Delivery Convection-enhanced delivery, pioneered by Bobo et al., delivers agents directly into the tumor and the surrounding Inhibitors,research,lifescience,medical parenchyma with continuous, positive-pressure infusion [3]. While other methods of delivery exist, such as through intraarterial and intrathecal routes, these are often limited by the blood-brain and blood-CSF

barrier as well as unwanted toxicities. Furthermore, compared to diffusion-based drug delivery (i.e., carmustine wafers), convective Montelukast Sodium delivery Abiraterone allows for larger volumes of distribution, as it is not limited by diffusive spread by concentration gradients [4]. Importantly, CED allows direct access to the tumor bed, achieving high local concentrations of drug with minimal systemic absorption. One of the first therapeutic agents given via CED for malignant gliomas in a clinical trial was diphtheria toxin conjugated to transferrin (TF-CRM107) [9]. This pioneering clinical trial highlighted the capability of CED to maximize therapeutic effect while limiting toxicity, as adverse events were limited.