A new drug from Northwestern University shrinks an incurable form of brain cancer in mice, paving the way for a possible therapy for this devastating disease.
Due to their seclusion, buried deep within fragile cerebral tissue and locked behind the fortress that is the skull, brain tumors are often tough to remove by surgery and other standard methods of cancer therapy.
This dearth of a good remedy is especially poignant for glioblastoma multiforme (GM), a highly aggressive brain tumor that grows quickly and can reach an enormous size before developing symptoms.
All cancers are caused by gene mutations, and the researchers devised a cutting-edge strategy to target the ones responsible for the aggressive growth of glioblastoma tumors.
They used spherical bullets made of gold nanoparticles and genetic material called RNA to manipulate the mutated GM genes that were running amok. RNA is a close cousin to the more widely known DNA, and certain varieties of this material can turn genes on and off.
The nano-sized balls of RNA are small enough to sneak through the blood brain barrier, a natural filter that protects the mind from harmful compounds in the bloodstream but can also impede life-saving drugs.
"This is a beautiful marriage of a new technology with the genes of a terrible disease," said senior co-author Dr. Chad Mirkin, a nanomedicine expert and professor of chemistry at Northwestern.
Mirkin perfected the technique for creating spherical balls of RNA in 1996, and then teamed up with glioblastoma expert Dr. Alexander Stegh, also of Northwestern, who in 2007 discovered a mutation that helps the cancer resist conventional chemotherapies.
"My research group is working to uncover the secrets of cancer and, more importantly, how to stop it," said Stegh, a senior co-author on the study. “The beauty of the gene we silenced – Bcl2Like12 – is that it plays many different roles in therapy resistance. Taking the gene out of the picture should allow conventional therapies to be more effective.”
Switching off the Bcl2Like12 gene reduced tumor size 3-4 fold in mice and increased their survival rate by 20 percent, the report states.
Glioblastoma is a very challenging cancer, and most chemo-therapeutic drugs fail in the clinic, according to Stegh.
“One problem is there is a large list of genes that are somehow disregulated in glioblastoma, but we have absolutely no way of targeting all of them using standard pharmacological approaches,” Stegh said. “We think nanomaterials can play a fundamental role in allowing us to implement the concept of personalized medicine in cancer therapy.”
The nanoparticles were also equipped with a tracker — gadolinium — that permits detection by cerebral MRI scans. Here is a 3-D reconstruction of magnetic resonance images after intracranial injection of gadolinium-functionalized spherical nucleic acids.
Video courtesy of Science Translational Medicine/AAAS and Jensen SA, Day ES, Ko CH, et al. 2013.
Source: Jensen SA, Day ES, Ko CH, et al. Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma. Science Translational Medicine. 2013.