NU 2015-098
Inventors
Leonidas C. Platanias*
Gary E. Schiltz
Rama K. Mishra
Short Description
A small molecule to treat glioblastoma multiforme by blocking the Mnk pathway.
Background
Glioblastoma multiforme (GBM) is an aggressive brain cancer associated with a low survival rate, high recurrence, and limited therapeutic options. Most diagnosed patients die within one year, even with treatment, thus there is a strong need for effective therapeutics. Current treatment options include Avastin, a drug that starves the tumor of a blood supply, and Gliadel® Wafer, a chemotherapeutic-infused wafer placed at the tumor site after surgical resection. Additional approaches being explored include the targeting of pre-cancerous stem cells in order to reduce the recurrence rate of GBM. As an active player in cancer progression in neuronal precursors, the enzyme Mnk may promise to be an effective target for treating GBM.
Abstract
Researchers at Northwestern University have developed a small molecule for the treatment of glioblastoma multiforme (GBM). This novel inhibitor targets the enzyme Mnk, an important player in cancer cell proliferation whose inhibition results in potent anti-tumor effects. In addition to its promising effects in cancer, Mnk inhibition is also correlated with beneficial improvement in neuronal pathologies arising from Alzheimer’s disease and Fragile X syndrome, suggestive that Mnk may be an attractive target for multiple indications. In vitro studies show that Mnk inhibition blocks the continued growth of cancerous neuronal precursors. While the inhibitor alone exhibits anti-tumor effects in GBM, it may also be useful in combination therapy, as it improves the anti-tumor effects of chemotherapeutic agents for other cancers as well (e.g. breast cancer, lung cancer). Other Mnk inhibitors exist, however, they exhibit either modest potency, non-selectivity, or significant toxicity. This newly identified compound is a potent inhibitor of Mnk kinase, possesses drug-like properties and selectivity suitable for a potential therapeutic, and has low toxicity, making it an attractive molecule to develop into a drug.
Applications
Advantages
Publications
Bell JB, Eckerdt FD, Alley K, Magnusson LP, Hussain H, Bi Y, Arslan AD, Clymer J, Alvarez AA, Goldman S, Cheng SY, Nakano I, Horbinski C, Davuluri RV, James CD, Platanias LC (2016) MNK inhibition disrupts mesenchymal glioma stem cells and prolongs survival in a mouse model of glioblastoma. Molecular Cancer Research, 14: 984-993.
IP Status
Issued US Patent No. 10,093,668
MRI of brain tumor in GBM patient. Image from The Cancer Genome Atlas.