A collaborative effort between the Mayo Clinic, The University of Texas at Austin, Harvard University, Howard Hughes Medical Institute and Boston University have developed an injectable therapy that reverses cancer in mice. Researchers first identified a breast-cancer-promoting gene and then specifically targeted this gene with nanoparticles that carry RNA gene-silencing snippets to treat breast cancer. This may develop into a new non-surgical therapy option for patients diagnosed with early-stage breast cancer.
According to Hu Li, Ph.D., Mayo Clinic pharmacologist and a co-first author on the study, “Precancerous cells are at a tipping point, in which they could become full-blown cancer or not. Our results show that, if we know the right target genes, it is possible to tip the balance in favor of a more normal cell state, preventing cancer progression, and improving survival outcomes.”
Researchers developed a computational approach to identify cancer-related changes in regulatory genes which in turn control many other genes. This aided in finding the most-significant genes that turn normal breast cells into tumor cells. It is believed that targeting these regulatory genes could have a dramatic effect on cancer cells based on all of the downstream genes which would also be affected. Researchers homed in on a specific regulatory gene known as HoxA1 as a driver of breast cancer in mice with a high rate of hereditary breast tumors.
Researchers looked at HoxA1 to see if it could be down-regulated to prevent further tumor development in mice within the cells where the tumor develops. To do so, the Wyss Institute team injected nanoparticles carrying a gene-silencing snippet of RNA directly into the nipples of mice. This allowed the nanoparticles to enter the entire milk-duct network.
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The nanoparticles were small fat-based particles which were coupled to molecules specifically designed to down-regulate HoxA1. To reduce possible toxicity, the team decided to inject the particles directly into the breast ducts where tumors form instead of injecting systemically. The team found that mice developed dramatically fewer tumors with this therapy. They also discovered that depletion of HoxA1 appeared to reverse tumor characteristics tipping the scale of cellular balance back to a normal cell state.
There is a current triple negative breast cancer clinical trial underway nationwide to test a new breast cancer treatment. Click the map below for more information:
With further advancements in this approach, researchers suggest that it may be possible to identify the best therapeutic gene targets specific to and individual patient’s tumor making this a tumor-specific and patient-specific treatment.
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