Attaching anti-cancer drugs to a common protein and making a ‘poison pill’ that cancer cells take in could increase the effectiveness of chemotherapy, according to researchers at Massachusetts General Hospital (MGH).
In order to kill cancer cells effectively, enough anticancer drugs need to be delivered into a tumour as possible, which is often difficult. A new approach involves binding the drugs to albumin, the most abundant protein in blood. Tumours have a strong appetite for protein nutrients to fuel malignant growth. When they consume albumin, the tumour will also take in the drugs bound to this protein.
One commonly used albumin-bound drug is nanoparticle albumin-bound paclitaxel (nab-PTX), which has been successfully used in the treatment of advanced lung and pancreatic cancers. “Not all patients respond to nab-PTX, though, and the effectiveness of its delivery to tumours has been mixed, owing to an incomplete understanding of how albumin impacts drug delivery and actions,” said senior author Miles Miller, PhD, a principal investigator in the MGH Center for Systems Biology and assistant professor of Radiology at Harvard Medical School.
To improve their understanding, Prof Miller and colleagues examined the delivery of nab-PTX to tumours at a single-cell resolution in mouse models of cancer. Using 3D microscopy and tissue clearing technology, the team found that cancer cells can take up a significant amount of nab-PTX. They also found that the consumption of these drugs is controlled by signaling pathways involved in the cells’ uptake of nutrients such as 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,” explained Ran Li, PhD, first author on the study and an instructor in the MGH Department of Radiology and the Center for Systems Biology. Indeed, treating tumours with an inhibitor of insulin-like growth factor 1 receptor, an important component of one of the signaling pathways, improved the accumulation of nab-PTX in tumours and boosted its effectiveness.
“These results offer new possibilities to improve delivery of albumin-bound drugs in patients with diverse types of cancer,” said Prof Miller.
Source: Phys.Org
Journal information: Ran Li et al, Therapeutically reprogrammed nutrient signalling enhances nanoparticulate albumin bound drug uptake and efficacy in KRAS-mutant cancer, Nature Nanotechnology (2021). DOI: 10.1038/s41565-021-00897-1
