New research led by a team at Massachusetts General Hospital (MGH) points to a promising strategy for stimulating the uptake of anticancer drugs by tumors, thereby increasing the effectiveness of chemotherapy treatments. The group’s results are published in Nanotechnology of nature.
Getting enough anticancer drugs into a tumor is often difficult, and a potential strategy to overcome this challenge is to bind the drugs to albumin, the most abundant protein in the blood. The strategy relies on the tumors’ great appetite for protein nutrients that fuel malignant growth. When consuming available albumin, tumors will inadvertently absorb the attached drugs.
A popular albumin-related drug approved by the United States Food and Drug Administration is nanoparticulate albumin-bound paclitaxel (nab-PTX), and it has been used successfully to treat lung and pancreatic cancers. at an advanced stage. “However, not all patients respond to nab-PTX and the efficacy of its administration to tumors has been mixed, due to an incomplete understanding of the impact of albumin on drug delivery and actions. “Says lead author Miles Miller, PhD, Principal Investigator. at the MGH Center for Systems Biology and Assistant Professor of Radiology at Harvard Medical School.
To provide information, Miller and colleagues evaluated the administration of nab-PTX to tumors at single cell resolution in mouse models of cancer. Using 3D microscopy and what is called tissue compensation technology, the team found that cancer cells can take up a significant amount of nab-PTX and that the consumption of these drugs is controlled by signaling pathways involved in nutrient uptake by cells. in the form of 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 increasing their intake of nab-PTX,” says Ran Li, PhD, lead author of study and an instructor in the MGH’s Department of Radiology and the Center for Systems Biology. Indeed, treatment of tumors with an insulin-like growth factor receptor 1 inhibitor, an important component of one of the signaling pathways, enhanced the accumulation of nab-PTX in tumors and increased its efficiency.
“These results offer new possibilities for improving the delivery of albumin-related drugs in patients with various types of cancer,” says Miller.
Co-lead author Ralph Weissleder, MD, PhD, is director of the MGH Center for Systems Biology. Other MGH co-authors include Thomas Ng, MD, PhD, Mark Prytyskach, Chris Rodell, PhD, Hannes Mikula, PhD, Rainer Kohler, PhD, Michelle Garlin, MD, Sareh Parangi, MD, Nabeel Bardeesy, PhD , and his colleagues from several other institutions.
This work was supported by the National Institutes of Health, the National Cancer Institute, the National Science Foundation, the American Cancer Society, the American Thyroid Association, and the Thyroid Cancer Survivors’ Association.
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