New research from Massachusetts General Hospital (MGH) reports on a development in improving the effectiveness of chemotherapy. The technique works by binding albumin to chemotherapy drugs, which causes cancer cells to attach to them.
This strategy has already been approved for a nanoparticle albumin-bound paclitaxel (nab-PTX) that treats late-stage lung and pancreatic cancers. But, explains senior author Miles Miller, PhD, "Not all patients respond to nab-PTX, though, and the effectiveness of its delivery to tumors has been mixed, owing to an incomplete understanding of how albumin impacts drug delivery and actions.” Miller is a principal investigator in the MGH Center for Systems Biology and an assistant professor of Radiology at Harvard Medical School.
In order to address this lack of understanding, the researchers employed 3D microscopy and tissue clearing technology in mice models to analyze the uptake of nab-PTX by cancer cells. They observed how the consumption of nab-PTX is controlled by signaling pathways that are related to the uptake of certain nutrients - particularly albumin.
"This discovery suggested that if we could manipulate these pathways, we might be able to trick cancer cells into a nutrient-starved state, thereby enhancing their consumption of nab-PTX," explains first author Ran Li, Ph.D., who is an instructor in the MGH Department of Radiology and the Center for Systems Biology. The team’s subsequent testing proved this hypothesis.
The findings are published in the journal Nature Nanotechnology. "These results offer new possibilities to improve delivery of albumin-bound drugs in patients with diverse types of cancer," concludes Miller.