PROJECT SUMMARY
Currently, there are few options for treating diffuse cancers. This is a particular challenge
for diffuse cancers that arise in sensitive tissues (i.e., not amenable to resection), in tissues in
which drug diffusion is limited, or in patients for whom typical interventions incur unacceptable
sequelae (e.g., pediatric patients).
Here, we investigate a novel approach: guiding cells with electrical fields (electrotaxis) to
consolidate the diffuse cancer cells to one or few locations (making them less diffuse), or
alternately, move these cells to a less critical location. As a basis for our approach, we will use
one of the most aggressive forms of pediatric brain tumor, Diffuse Intrinsic Pontine Glioma
(DIPG), which is emblematic of the challenges inherent in treating diffuse cancers. The need for
new treatments for DIPG is particularly critical, as it arises in the pons–a site that hosts critical
centers for breathing, chewing, heartbeat and swallowing–and incurs a dismal median survival
time of 9 months and is fatal in more than 99% of patients.
We propose to quantify, using transcriptomics and pharmacological inhibition, underlying
mechanisms of electrotactic tumor cell response. This will reveal electrotactic drug targets and
provide controls to manipulate/enhance further electrotaxis. We will investigate in vivo, the
effects of various electrode montages to shape and steer infiltrative DIPG cells in both the
cortex and pons. To support our approach, we will apply computational methods to iteratively
model and design stimulation montages in response to observed patterns of growth after field
application. These studies will provide a novel approach to addressing the general problem of a
diffuse cancer so that they can become more amenable to standard-of-care therapies.