Uproot myeloma
Designer DNA molecule helps to track down cancer stem cells in the blood
Roman Fandorin, "Newspaper DAILY"
Like weeds that grow back if you don't remove the roots, cancer can keep coming back thanks to hidden stem cells.
Now researchers have developed a "designer" DNA segment that can destroy these cancer stem cells, and tests on mice have shown promising first results in preventing cancer from returning.
Multiple myeloma is a cancer of blood plasma cells in which abnormal antibodies are produced and accumulated in the body, which eventually damage bones and kidneys and affect the body's ability to fight infection. Unfortunately, after treatment, patients usually relapse, and, even worse, the cancer often becomes resistant to previously successful treatments. This is due, at least in part, to the proliferation of myeloma stem cells, which can produce new cancer cells after the old ones are destroyed during treatment.
In previous studies, overexpression of the IRF4 protein has been associated with lower survival in patients with multiple myeloma because it increases the proliferation of myeloma stem cells. So, in a new study, researchers from the University of California, San Diego (UCSD) and Ionis Pharmaceuticals decided to silence the gene encoding this protein.
To do this, they developed a so-called antisense oligonucleotide, a constructed fragment of DNA that binds to a specific gene. This particular oligonucleotide is called ION251, and it is designed to target the IRF4 gene. This helps to destroy not only malignant plasma cells, but also myeloma stem cells to prevent the disease from returning.
The team tested ION251 on modified mice with transplanted human myeloma cells. Each group included 10 mice who received doses of the drug or placebo every day for the first week, and then three doses per week until the end of the study.
Article by Mondala et al. Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption published in the journal Cell Stem Cell – VM.
Microscopic images of the bone marrow of mice with multiple myeloma; red dots represent the IRF4 protein. On the left – the mouse from the control group, on the right – the one receiving treatment. Figure from the press release of UCSD Designer DNA Therapeutic Wipes Out Cancer Stem Cells, Treats Multiple Myeloma in Mice - VM.
The team also states that ION251 can be used in combination with more traditional cancer treatments, making tumors more sensitive to them and hopefully preventing relapses.
Phase I clinical trials are already underway to evaluate the safety and efficacy of ION251 in humans.
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