New research from the University of Pennsylvania's School of Veterinary Medicine has identified an FDA-approved drug that, when used with surgery, hampers metastasis in an animal model. Originally developed and approved nearly 65 years ago to control blood pressure, the medication resperine also prevents what are known as tumor-derived extracellular vesicles (TEVs) from fusing to healthy cells and sharing their cargo of disease-promoting molecules, the research team found.
"No matter what we do to kill cancer cells -- surgery or radiotherapy or chemotherapy -- causes stress, and the data show that the stress can stimulate production of these vesicles," says Serge Fuchs, a biologist at Penn Vet. "So our thinking is, as an adjuvant to that primary treatment, it would be prudent to limit the effect of these vesicles on healthy tissues, thereby preventing the spread of malignant cells."
Study - Findings - Journal - Cancer - Cell
The study's findings, published in the journal Cancer Cell, show that giving moderate doses of resperine to mice with melanoma prior to and following surgery disrupted the uptake of TEVs by healthy cells, reduced the spread of the cancer, and significantly prolonged survival in the animals.
While previous research had shown that TEVs encourage metastatic disease and, in some circumstances, can transform normal cells into malignant ones, it's clear that not every healthy cell that comes into contact with these vesicles becomes cancerous. Thus scientists have hypothesized that healthy cells may possess a strategy to defend themselves against this transformation. Such a defense mechanism could be a target for anti-metastatic therapies.
Search - Players - Defense - Fuchs - Colleagues
In search of the players in a putative defense, Fuchs and colleagues looked to see which surface proteins on human cells changed in number upon exposure to TEVs from melanoma cells. One of the more significant to undergo a change was IFNAR1, one of the proteins that compose the type I interferon receptor, a...
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