In order for the disease to spread, it needs to set up a hospitable environment in distant organs. To make them fertile for circulating malignant cells, the tumor sends out small vehicles from the primary point. Blocking this mechanism that prepares the target tissues for cancer cells to seed and thrive could reduce cancer’s lethality.
Researchers from the University of Pennsylvania’s School of Veterinary Medicine have identified an FDA-approved drug that, when used with surgery, was able to hamper metastasis in tests with animal models. When it was developed, nearly 65 years ago, Reserpine was meant to control blood pressure, but now scientists have found that it can also prevent tumor-derived extracellular vesicles (TEVs) from binding with healthy cells.
“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”, explained biologist Serge Fuchs. “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”.
The team reported that moderate doses of Reserpine administered before surgery “disrupted the uptake of TEVs by healthy cells, reduced the spread of the cancer, and significantly prolonged survival” in their testing.
As not all healthy cells transform into malignant ones in contact with these vesicles, it became apparent that there is a hidden mechanism of defense against this change. This is how they ended up looking at IFNAR1, one of the proteins that compose the type I interferon receptor, and a common medication for cancer treatment.
Laboratory experiments using human cells revealed that human melanoma patients with metastatic disease were more likely to have lower levels of IFNAR1. Testing confirmed that mice that received the reserpine treatment before and after surgery seemed to disrupt the reprogramming of healthy cells. Survival rates for these animals significantly improved, and the treatment “virtually eliminated” evidence of lung metastases.
The team’s objective is to extend research not only on the effect of Reserpine on metastasis but also on vesicle formation and composition.
These findings could revolutionize cancer treatments and save countless lives.
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