Scientists at the OSUCCC – James found that this drug, used to treat many types of solid tumors and blood cancers, can enter heart cells by hitchhiking on a specific protein that functions as a transporter to move a drug from the blood into heart cells.
By introducing another anticancer drug in advance of the chemo, the researchers were able to block the transporter protein, effectively stopping the delivery of doxorubicin to those cardiac cells. This added drug, nilotinib, has been previously found to inhibit activation of other related transport proteins.
The current findings are based on lab experiments in cell cultures and mice. The researchers are continuing studies and hope to start designing human trials of the drug intervention later in 2021.
“The proposed intervention strategy that we’d like to use in the clinic would be giving nilotinib before a chemotherapy treatment to restrict doxorubicin from accessing the heart,” says first author Kevin Huang, who recently earned a PhD in pharmaceutical sciences at Ohio State and is a former Pelotonia Fellow. “We have solid preclinical evidence that this intervention strategy might work.”
The study was published in January in the journal Proceedings of the National Academy of Sciences.
Doxorubicin is known for its potential to increase patients’ risk for serious heart problems, with symptoms sometimes surfacing decades after chemo, but the mechanisms have been a mystery. The risk is dose-dependent — the more doses a patient receives, the higher the risk for future cardiac dysfunction, including arrhythmia and a reduction in blood pumped with each contraction, a symptom of congestive heart failure.
Huang worked in the lab of senior study authors Shuiying Hu, PhD, and Alex Sparreboom, PhD, faculty members in the Division of Pharmaceutics and Pharmacology at Ohio State, and members of the Translational Therapeutics Program at the OSUCCC – James. This research and other studies targeting transport proteins to prevent chemo-related nerve pain were also part of Huang’s dissertation.
“Our lab works on the belief that drugs don’t naturally or spontaneously diffuse into any cell they would like to. We hypothesize that there are specialized protein channels found on specific cells that facilitate movement of internal or external compounds into the cell,” Huang says.