Among cancers, liver tumors have been particularly hard for doctors to treat. The cancer cells tend to be hardy from the beginning and even undergo changes that make them more resistant to chemotherapies. What’s clear is that an effective treatment needs to reach the cancer cells, and not affect or damage the normal liver.
The trick, however, is getting drugs to the tumor. Researchers have been pinning hopes on getting drugs to cancer sites using the body’s own messaging system—extracellular vesicles, or EVs—tiny pouches released by cells that typically carry molecular messages from one cell to another.
In his lab, Tushar Patel, M.B., Ch.B., dean for research at Mayo Clinic’s Florida campus, investigates using these EVs as a way to deliver drugs and treatments into cancer cells. “EVs are released by many types of cells, and can even be found in most if not all bodily fluids,” he explains. “But in order to use them for cancer treatment, large quantities of EVs need to be available.”
In a recent paper in Laboratory Investigation, Dr. Patel’s team showed that EVs could be obtained from milk, and then used to deliver treatments to the cells of hepatocellular carcinoma, a primary liver tumor that can be caused by cirrhosis. Cow’s milk—like human milk—has been known to contain EVs. Using EVs from milk has been an intriguing area of study, says Dr. Patel, and they can be easily isolated in large quantity.
Dr. Patel’s lab developed a process to isolate the EVs from casein protein in skim milk and use them for drug delivery. In laboratory tests, the team found that milk-derived EVs could be used to deliver chemotherapy as well as a new type of treatment based on using RNA molecules, known as an antisense nucleotide, into liver cancer cells, causing the cells to die. Researchers also found the treatment shrank tumors in mice. “The study suggested that the use of milk-derived nanovesicles may be a promising approach for delivering drugs to liver tumors,” he says.
“These results are very preliminary,” Dr. Patel says, adding that his lab is also investigating any potential harmful effects of using these milk-derived nanovesicles. “We want to know whether we can manipulate the proteins on the vesicles so that they will more directly recognize the tumor cells, even for a particular tumor type. Ultimately, we also want to know whether we can deliver this type of treatment orally and have the same kind of effect.” Future studies will aim to refine the use of milk-derived EVs for drug delivery with the eventual goal of taking these into clinical trials.
The research was funded in part through the Office of the Director, National Institutes of Health and the National Center for Advancing Translational Sciences, as well as through the Mayo Clinic Center for Regenerative Medicine.
Other researchers are Joseph George, Ph.D., currently of the Kanazawa Medical University, Japan, and Irene K. Yan of Mayo Clinic.
- Cell Biology Program
- Discovery and Translation Labs – Florida
- Gastrointestinal Cancer Program
- Mayo Clinic Cancer Center
- Molecular Hepatology Laboratory