A completely new approach to cancer treatments has been developed by researchers from the University of Tokyo, Japan — and it could bring about a new era of drug development. It involves artificial, hairpin-shaped strands of DNA that react with specific microRNA that are over-produced in cancer cells, triggering a natural immune response. In lab tests, the technique was found to be effective against malignant melanoma cells from mice as well as human breast- and cervical cancer-derived cells.
Drugs based on nucleic acids — specifically the information-carrying molecules deoxyribonucleic acid (DNA) and ribonucleic (RNA) — have the ability to control the biological functions of cells.
Because of this, their development is expected to transform the future of medicine, and provide new avenues for the treatment of cancer and other hard-to-treat illnesses caused by genetic diseases and viruses.
In their study, bioorganic chemist Professor Akimitsu Okamoto of the University of Tokyo and his colleagues were inspired to create a new anticancer drug using artificial DNA.
Paper author and bioorganic chemist Professor Akimitsu Okamoto of the University of Tokyo said: “We thought that if we can create new drugs that work by a different mechanism of action from that of conventional drugs, they may be effective against cancers that have been untreatable up to now.”
Developing nucleic acid drugs for use in the treatment of cancer has to date been a challenge — in part because it is difficult to make nucleic acids distinguish between cancer cells and their healthy counterparts.
This means that there has traditionally been a risk that the treatment would inadvertently target healthy cells and negatively impact the patient’s immune system.
In their study, however, Prof. Okamoto and his colleagues synthesised a pair of hairpin-shaped, cancer-killing pieces of DNA — dubbed “oHPs” — that work by triggering a natural immune response and only target specific cancer cells.
Cancer can cause cells to overexpress — that is, to make too many copies of — certain DNA and RNA molecules, causing them to function improperly.
Once injected into the target cells, the researchers’ artificial DNA strands work by connecting to one such overexpressed microRNA molecule called miR-21 — and then unravelling.
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This unravelling allows the oHps to join together to form longer chains of DNA, which in turn triggers the immune system to recognise the overexpressed miR-21 molecules as dangerous — activating an innate immune response that not only kills the cancer cells, but also prevents further growth of cancerous tissue.
In laboratory tests, the team found that the oHps were effective against overexpressed miR-21 in both human cervical cancer-derived cells, human triple-negative breast cancer-derived cells and mouse malignant melanoma-derived cells.
Prof. Okamoto: “The formation of long DNA strands due to the interaction between short DNA oHPs and overexpressed miR-21, found by this research group, is the first example of its use as a selective immune amplification response which can target tumour regression.”
This, he added, is “providing a new class of nucleic acid drug candidates with a mechanism that is completely different from known nucleic acid drugs.”
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Okamoto continued: “The results of this study are good news for doctors, drug discovery researchers and cancer patients, as we believe it will give them new options for drug development and medication policies.
“Next, we will aim for drug discovery based on the results of this research, and examine in detail the drug efficacy, toxicity and potential administration methods.”
The researchers cautioned, however, that there are “many steps to go” before a treatment for cancer based on their technique can be made widely available.
The full findings of the study were published in the Journal of the American Chemical Society.
