Malaria Drug Chloroquinone Inhibits Autophagy and Enhances Vemurafenib Treatment of BRAF+ Glioblastoma

After her brain cancer became resistant to chemotherapy and then to targeted treatments, 26-year-old Lisa Rosendahl's doctors gave her only a few months to live. Now, a paper published online on January 17,2016 in the journal eLife describes a new drug combination that has stabilized Rosendahl's disease and increased both the quantity and quality of her life: adding the anti-malaria drug chloroquine to her treatment stopped an essential process that Rosendahl's cancer cells had been using to resist therapy, re-sensitizing her cancer to the targeted treatment that had previously stopped working. Along with Rosendahl, two other brain cancer patients were treated with the combination (vemurafenib and chloroquinone) and both showed similar, dramatic improvement. The eLife article is titled “Autophagy Inhibition Overcomes Multiple Mechanisms of Resistance to BRAF Inhibition in Brain Tumors.” "When I was 21 they found a large mass in my brain and I had it resected right away. They tested it for cancer and it came back positive," Lisa says. "Lisa is a young adult with a very strong will to live. But it was a high-risk, aggressive glioblastoma and by the time we started this work, she had already tried everything. For that population, survival rates are dismal. Miraculously, she had a response to this combination. Four weeks later, she could stand and had improved use of her arms, legs and hands," says paper first author Jean Mulcahy-Levy (photo), M.D., investigator at the University of Colorado Cancer Center and pediatric oncologist at Children's Hospital Colorado. The science behind the innovative, off-label use of this malaria drug, chloroquine, was in large part built in the lab of Andrew Thorburn, Ph.D., Deputy Director of the CU Cancer Center, where Mulcahy-Levy worked as a postdoctoral fellow, starting in 2009. Dr.
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