Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites

What is it about?

Treating tumors that spread from other organs to the brain can be challenging because common medications are often blocked by the nearly impenetrable membrane that separates the brain from the rest of the body, making it difficult for treatments to reach the affected area. The most common sources of metastatic brain tumors are breast, lung, and colon cancers. What’s needed is therapeutics that can combat against the metastasized tumor in the brain – and better yet, one that can simultaneously treat the cancer at the source.

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Why is it important?

Removing tumor cells that have spread to the brain is challenging with surgery, and treating highly aggressive brain cancers using systemic medications is hindered by the selective permeability of blood brain barrier and their limited effectiveness against both peripheral and brain tumors. We developed a nanoparticle made of a biodegradable polymer that could simultaneously deliver metabolic inhibitors to the brain and the peripheral tumor. We coupled it with previously developed prodrugs that take aim at cancer cells’ energy source, the mitochondria and inhibits the energy production pathways. In preclinical studies, the combined drugs were able to shrink both primary breast cancer tumor and breast cancer cells that were seeded in the brain to form tumors. We plan to advance these studies toward clinical trials, with the hope that this may eventually provide an effective, single-approach treatment for patients whose cancers have spread to the brain.