Genetic Discovery May Be ‘Super Assassin’ of Tumor Cells, Researcher Says

Genetic Discovery May Be ‘Super Assassin’ of Tumor Cells, Researcher Says

The nucleotide expansions that cause a number of degenerative diseases may be the reason why these patients are far less susceptible to cancer, a new study suggests. A leading researcher says this discovery represents a “a super assassin against all tumor cells,” including those in ovarian cancer.

Researchers found that repeated CAG (cytosine-adenine-guanine) sequences in the huntingtin gene, which cause Huntington’s disease, produce small RNA molecules that attack genes critical for cancer cell survival.

These RNA molecules slowed tumor growth in several cancer mouse models, suggesting their potential as a new anti-cancer approach.

The study, “Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells,” was published in EMBO Reports.

Patients with Huntington’s and other degenerative diseases are roughly 80 percent less likely to develop cancer. Some studies have attributed this to the presence of trinucleotide (TNR) expansions.

TNR expansions are a type of mutation where three nucleotides are repeated numerous times. Besides Huntington’s, these expansions are responsible for many degenerative diseases, such as spinocerebellar ataxias, and spinobulbar muscular atrophy.

These triplet motifs can be amplified not only in the gene coding region of DNA, but also in non-coding regions. In this cases, the repeats can form specific RNA structures that function much like small-interfering RNA (siRNA), targeting key survival genes. siRNA molecules have the ability to bind RNA molecules — the intermediate product between a gene and a protein — and prevent their expression.

Researchers have now identified a family of TNR-based siRNAs that could effectively kill tumor cells. Importantly, they found that the siRNAs could be delivered to tumor cells as a molecule.

In a panel of mouse or human cancer cell lines, the siRNAs were between 10 and 100 times more toxic compared to other siRNAs previously shown to inhibit cell growth.

The reason for this enhanced killing, the investigators suggest, is because these TNRs are present in many cancer-causing genes, and a single molecule can simultaneously target multiple survival genes.

To further test their molecule, researchers used a mouse model of ovarian cancer. To effectively deliver the molecule, they inserted the siRNA in nanoparticles.

The approach delayed tumor growth by five to six days, with no major toxicity to normal cells. Importantly, the cancer cells did not become resistant to this type of therapy.

“This molecule is a super assassin against all tumor cells. We’ve never seen anything this powerful,” said lead study author Marcus Peter, PhD, in a press release. Peter is the Tom D. Spies Professor of Cancer Metabolism at Northwestern University Feinberg School of Medicine.

Further studies are now needed to find better ways to deliver these siRNAs to tumour sites, researchers said.

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