Cancer is characterized by cells that divide and grow uncontrollably, creating tumors. Researchers have shown that a new cancer therapy, which was tested in mice, can slow or stop the division of cancer cells, and the growth of tumors. The therapy is a microRNA called miRNA-34a, and it significantly reduces the expression of at least three genes, AXL, CD44, and MET, which are known to promote cancer cell growth. The treatment works for at least five days, halting cancer cell division and stopping tumors from growing. In a 21-day trial, tumors in one group of mice given the treatment did not get any bigger, while tumors in untreated mice got three times larger. The findings, which are patent-pending and could eventually be a new cancer treatment for patients, have been reported in Oncogene.
This new technology utilizes a powerful microRNA along with a successful delivery system that specifically targets cancer cells. The treatment is like brakes on a car, which slow or stop cell division, explained lead study author Andrea Kasinski, an Associate Professor at Purdue University.
"When we acquired the data, I was ecstatic," said Kasinski. "I am confident that this approach is better than the current standard of treatment and that there are patients who will benefit from this."
When genes are expressed, they are transcribed into RNA molecules. MicroRNAs are short strings of RNA; miRNA-34a is commonly found in cells at high levels, but in many types of cancer cells, those levels are significantly reduced.
Researchers thought that cancer cell division could be stopped, and tumor growth halted, by raising the levels of miRNA-34a. However, RNA also degrades quickly, so scientists had to find a way to sustain the molecule while delivering it to the right place. The team applied chemical modifications that have been developed for other technologies, and tested them in mouse models. This work showed that the chemically modified miRNA-34a could hang around for 120 hours or more after being used as a treatment. The microRNA also does not provoke the immune system, which often reacts to foreign miRNAs.
To make the treatment specific to cancer cells, the researchers added the vitamin folate to the miRNA. While many if not all cells are able to absorb folate, cells of many cancer types have far more folate receptors on their surfaces compared to heathy cells. The tiny miRNA-34a-folate complex can move into tumors and attach to tumor cell surfaces. The cancer cells take up the complex, which then slows cell division and tumor growth.
The investigators said that the therapy will be specific enough to avoid unintended, toxic effects to other cells. Because the folate makes the treatment more selective, the researchers suggested that less of it will be needed for it to be effective, which could keep costs low and further reduce the likelihood of side effects. The therapy can also be modified without folate so that it targets other cell surface receptors that are found on different cancer types. Now, further testing will be needed to determine if it is effective in people.