In the world of cancer, in which the word ‘frightening’ takes on entirely new perspectives, perhaps none is more frightening than brain cancer. Although brain cancer is not one of the leading types of cancer per capita, the brain’s absence of pain receptors can hide the cancer’s growth and effects and it is often left undiagnosed until it has grown dangerously large. Maybe our fear has to do with the turbid violation of our innermost self, our control center; or maybe it is those subtle (or not so subtle changes) that make us question whether we’re losing our mind or if there is actually something physically wrong. Regardless, in our world of microscopic monsters, brain cancer is one of the most spine-chilling, nerve-wracking thoughts we have to deal with.
Glioblastoma multiforme (GBM) is a type of brain cancer which is technically rare, occurring in only 2-3 cases per 100,000, but represents just over half of all brain tissue tumors. The survival odds are bleak, with a median of only 1-2 years with typical care (surgery, radiation and chemotherapy) and 3 months without. GBM tend to form in the cerebral white matter and grow very quickly and may often cross bilaterally to the opposite hemisphere, but rarely extends beyond the central nervous system. The symptoms may include seizures, headaches, nausea and vomiting, but may also include memory loss or personality changes. GBM is traditionally difficult to treat for various reasons: including the brain’s susceptibility to damage from traditional care, the GBM tumor cells are resistant to some forms of traditional care, the brain has limited self-repairing abilities, and many drugs lose efficacy crossing (or just cannot cross) the blood-brain barrier.
Perhaps one of the biggest recent discoveries in cancer research has been Cancer Stem Cells (CSCs). CSCs are cancer cells which also possess characteristics associated with standard stem cells, specifically the ability to give rise to all cell types found in the tumor. They are believed to be tumor-forming, or tumorigenic, and may be one of the principle reasons why GBMs are so resistant to most chemo drugs. Their existence also explains many of the tendencies of some cancers, including metastasis and reoccurrence after seemingly successful treatments. Several developmental pathways have been implicated in CSC, including NOTCH and Sonic Hedgehog (SHH) and therapeutic recombinant proteins are being designed in attempt to target the undifferentiated cell populations in tumors. Among the more popular of these is from the super family of TGF-β. Within that family, a company called Genelux out of California is looking into a potential GBM CSC regulator with a growth factor called BMP4 (Bone Morphogenetic Protein-4).
In their recent publication, Rohit Duggal and associates expressed BMP4 in GBM models, showed significant tumor regression and a simply amazing increase in long-term survival of mice who had been inoculated with GBM and then treated with a VACV virus encoding BMP4. In the process, they utilized the firefly luciferase gene and some Luciferin to document the progression of GBM tumors in vivo mice brains, as compared to serum-grown glioma tumor line. With the bioluminescent marker encoded in the cancer cells, it becomes clear exactly how these cancers grow and spread in our system. I think this picture below sums up exactly why GBM cancer is so incredibly frightening.
This research is an early, proof of concept, experiment. There are many regulatory hurdles and trials before something of this nature could ever see medical treatment. Yet it provides hope; Hope that as we continue to discover more about how cancer originates and how it proliferates, we will learn how to treat this awful disease; Hope that we can beat this through scientific research; Hope that there is life after cancer and we will all know that someday. And if there is one thing that every cancer patient needs, it is Hope.
Duggal, R., Geissinger, U., Zhang, Q., Aguilar, J., Chen, N. G., Binda, E., Vescovi, A. & Szalay, A. A. (2013). Vaccinia virus expressing bone morphogenetic protein-4 in novel glioblastoma orthotopic models facilitates enhanced tumor regression and long-term survival. Journal of translational medicine, 11(1), 155.
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