A novel drug therapy based on nanoparticles is effectively treating mice with multiple myeloma, a cancer of bone marrow immune cells, Washington University in St. Louis researchers say.
Specifically designed to target the malignant cells, the nanoparticles guard their therapeutic load from degrading in the bloodstream, and enhance drug delivery into the cancer cells. In development of this class of potential cancer drugs, those are both longtime roadblocks.
The nanoparticles ferry a drug compound which stops a protein, called Myc, that is active in numerous types of cancer, including multiple myeloma.
Myc inhibitors are highly potent in a petri dish. But when they are injected into blood, they degrade instantly.
The chance that Myc inhibitors could be a viable treatment in patients has been problematic. Previous research in animals has shown that the compounds degrade too quickly to have any effect against cancer.
The study is the first to demonstrate that Myc inhibitors can be practical in treating animals with cancer, as long as the drugs have a vehicle to protect and deliver them into cancer cells.
Multiple myeloma is a cancer that attacks plasma cells. The cells are part of the immune system, and manufacture antibodies that fight off infection.
In multiple myeloma, however, plasma cells grow chaotically in the bone marrow, crowding out healthy cells. Treatments do exist, but only roughly 50 percent of patients with the disease survive five years past diagnosis.
“Today, we have half a dozen drugs for multiple myeloma that can put patients into remission,” says Tomasson, who treats patients with multiple myeloma at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.
“We also have new drugs in the pipeline that we hope will lengthen that remission. But for most patients, the cancer eventually comes back. With this type of targeted nanoparticle treatment, the hope is to be able to get rid of that last bit of residual disease, so the cancer can’t return.”
Nanomedicine expert Gregory M. Lanza, professor of science and practice of medicine, synthesized and modified a compound discovered by Edward V. Prochownik of the University of Pittsburgh.
The nanoparticles self-assemble, Lanza explains, comparing the process to shaking up an oil and vinegar salad dressing with a bit of mayonnaise to stabilize the tiny particles and the Myc inhibitor in the mixture.
“The nanoparticles serve as vehicles that protect the drug from the harsh environment of the blood,” Lanza says. “In this case, the drug is modified into a prodrug and actually locked into the outer membrane of the particle.”
Tomasson and Lanza note the therapy is still years away from being tested in people, but they are optimistic about its future potential and are eager to begin that work.
Deepti Soodgupta, Dipanjan Pan, Grace Cui, Angana Senpan, Xiaoxia Yang, Lan Lu, Katherine N. Weilbaecher, Edward V. Prochownik, Gregory M. Lanza, and Michael H. Tomasson
Small Molecule MYC Inhibitor Conjugated to Integrin-Targeted Nanoparticles Extends Survival in a Mouse Model of Disseminated Multiple Myeloma
Molecular Cancer Therapeutics, March 30, 2015; doi: 10.1158/1535-7163 MCT-14-0774-T
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