Teamwork toward a ‘Perfect Bullet’ for Leukemia
Imagine thatadrugis “oil”andthe human bodyis “water.”Aconduitwould beneeded to steer cancer drugsthrough the bodytoselectively targetcancer cells, wherever theyreside.
Ifa buddingWilmot Cancer Instituteinvestigation pans out, a nanoparticle-based delivery system might be exactlythe conduit thatscientists havebeen looking for, thetrio of young researcherssay.
Rudi Fasan, Ph.D., associate professor of Chemistry;Danielle Benoit, Ph.D., associate professor in the Department of Biomedical Engineering;andBen Frisch, Ph.D.,a research assistant professor in the Department of Medicine, Hematology/Oncology,are working together to improve the treatment ofacute myeloid leukemia (AML), one of the deadliest types of blood cancersbecause it often relapsesafter initial therapy.
They each bring a different scientific discipline and adistinct role to the project.
Fasan developsnew drugs and new methods to make them more effective. In this case, he discovered and modified asmall-moleculeanti-cancerdrug derived from a natural plant source related to the magnolia tree.After testingseveral different chemical forms of the compound,he is studyingthe correct potency andability topreciselydestroycancer cells.
Benoit’s nano-delivery system can transcendthebarriersthat sometimes prevent drugsfrom reaching their target.Nanoparticles are microscopic materials that act as a bridge between different structures—in this case the nanoparticles are designed to encapsulate an oily drug compound and make it more compatible with the body’s water. Her system also packages the drug with peptides (amino acids) that direct the treatment into the bone marrow, where leukemia takes root.
Getting to the root of the disease is important. Years ago, scientists discovered that leukemia most likely relapses because a subset of cells, known as leukemia stem cells, can dodge standard chemotherapy. Mature leukemia stem cells hide in the bone marrow in a quiet state, until they resurge. Wipingout these stem cells is the key to improving the treatment for a disease that can be very aggressive.
So far,scientists have notbeen able to target leukemia stem cells directlyin the bonemarrow,says Frisch, who studiesthe bone marrowenvironment for cluesasto why bloodcancersflourishthere.His roleis to takeFasan’s new drug, which will be loaded intoBenoit’s nano-delivery system,and conduct experiments in cell cultures and mice tofind out ifthe system is effective at binding to cancer cells.
“The idea is to have a perfect bullet,” Fasan says.“Avery nice feature of this collaboration is that we can take advantage of complementary expertise and run with it.”
“By using the proper materials to enhance drug delivery,” Benoit adds, “it could potentially revolutionize cancer treatment.”
The team won a2016-17 University Research Award. Funded annuallyby UR President Joel Seligman, the money goes to scientists with projectsthathave a high probability of receiving additional external funding.They received $75,000 to generatedata to compete for larger grants from the National Cancer Institute, the Leukemia and Lymphoma Society, and the Leukemia Research Foundation.