Study finds how microRNA therapy slows cancer tumour growth
Washington, US: Researchers at Purdue University have created a new cancer treatment that targets tumours by tricking cancer cells into ingesting a small piece of RNA that inherently prevents cell proliferation.
According to research published in Oncogene, whereas untreated tumours tripled in growth during the same 21-day study, tumours treated with the new medication did not grow in size.
Cancer can begin almost anywhere in the human body. It is characterized by cells that divide uncontrollably and that may be able to ignore signals to die or stop dividing, and even evade the immune system.
The therapy, tested in mouse models, combines a delivery system that targets cancer cells with a specially modified version of microRNA-34a, a molecule that acts “like the brakes on a car,” slowing or stopping cell division, said Andrea Kasinski, lead author and the William and Patty Miller Associate Professor of biological sciences at Purdue University.
The targeted microRNA-34a significantly inhibited the activity of at least three genes—MET, CD44, and AXL—known to promote cancer and resistance to other cancer treatments for at least 120 hours in addition to reducing or reversing tumour growth.
According to the findings, the patent-pending therapy, which is the most recent development in more than 15 years of research into using microRNA to kill cancer, may be efficient both by itself and in combination with currently available medications when used to treat malignancies that have developed drug resistance.
“When we acquired the data, I was ecstatic. I am confident that this approach is better than the current standard of treatment and that there are patients who will benefit from this,” said Kasinski, a member of the Purdue Institute for Cancer Research.
MicroRNA-34a is a short double strand of ribonucleic acid – a string of ribonucleic acids attached like the teeth of a zipper along the length of a sugar-phosphate chain. The two strings of the microRNA are unevenly zipped together, with one string acting to guide a protein complex to the worksite in the cell while the other string is destroyed.
In healthy cells, microRNA-34a is abundant, but its presence is dramatically reduced in many cancer cells.
While the idea of reintroducing microRNA-34a to cancer cells appears simple, the research team had to overcome many challenges in crafting an effective therapy. Naturally occurring RNA breaks down rapidly, so to improve the durability of the therapy, the team stabilized microRNA-34a by adding several small clusters of atoms along the length of the strand.
The team modelled its modifications on an FDA-approved chemical structure that researchers at the biotechnology company Alnylam used on similar short-interfering RNAs. Experiments on mouse models show the modified microRNA-34a endures for at least 120 hours after being introduced.
As a bonus, the fully modified microRNA-34a is invisible to the immune system, which would ordinarily attack double-stranded RNA introduced to the body.
To ensure the modified microRNA-34a makes it to cancer cells, the team attached the double strand to a molecule of the vitamin folate. The surfaces of all cells in our body have receptors that bind to folate and draw the vitamin into the cell, but the cells in many cancers – breast, lung, ovarian and cervical – have far more folate receptors on their cell surface than do healthy cells.
The tiny microRNA-34a and folate compound penetrates the dense tissue of tumours and binds to the folate receptor on the cell surface. It is then drawn inside a little bag of cell membranes called a vesicle. Once inside the cell, some of the microRNA-34a is able to escape the vesicle and slows cell division.
The targeted specificity of the therapy reduces the amount of the compound that must be administered to be effective, which in turn reduces potential toxicity, side effects and cost.
The team can also prepare a separate version, which targets a different cell surface receptor, for prostate cancer cells, which do not produce excessive folate receptors. Kasinski and her team are confident in the value of the most recent iteration and will prepare for clinical trials.
