A new study by researchers at Tel Aviv University has revealed a possible therapeutic pathway to keep osteosarcoma lesions in dormancy. Osteosarcoma is a form of cancer that develops in the bones of children and adolescents and is one of the most aggressive cancers known, with only a 15 percent, five-year survival rate in those diagnosed in the advanced metastatic stage. The new approach not only offers hope for reversing the spread of this cancer, it also provides effective science that can be used for nanomedicines tailored to keep cancer cells in a dormant, asymptomatic state.
"We want to keep the cancer 'switch' turned off," Ronit Satchi-Fainaro, who oversaw the research, said in a press release. "Once osteosarcoma metastasizes away from the primary tumor site, there is no effective treatment, just different ways of prolonging life."
The team used previous research on dormant tumor lesions in deceased people who were healthy until their deaths as the basis of their research and used it to analyze osteosarcoma recurrence and pinpoint the therapeutic value of dormancy.
Even when caught early, osteosarcoma tumors can return aggressively - in the case of "minimal residual disease," some cells left after surgery can suddently "turn on," leading to a reappearance of the disease, whereas in other cases of "dormant micrometastatic lesions," small tumors that are undetected by current technologies can turn into large cancerous growths.
"We wanted to understand what causes the cancer cells to 'switch on' in these cases," said Satchi-Fainaro. "As long as cancer cells remain asymptomatic and dormant, cancer is a manageable disease. Many people live with thyroid lesions without their knowledge, for example. Ours is a very optimistic approach, and we believe it could apply to other cancers as well."
The team used a mouse model to create osteosarcoma tumor tissues and examine them, eventually sequencing microRNAs in the tissues and identifying three that were expressed in low levels in the aggressive tumor tissues and in high levels in the dormant tumor tissues. Using these microRNAs, they inserted them into tumor tissues in a petri dish and observed their malignant potential.
"We saw that the osteosarcoma cells treated with the selected microRNAs were unable to recruit blood vessels to feed their growth," said Satchi-Fainaro. "In order to keep these microRNAs stable in the blood, we needed to encapsulate them in a nanoparticle that circulates in healthy blood vessels, but that disembark and deliver the drug therapy at the leaky blood vessels that exist at tumor sites. We designed a nanomedicine that would have a special activation method at the tumor site in the target cell."
The results were promising; mice treated with nanomedicine lived for six months, the equivalent of around 25 human years.
"This has huge potential, because the insertion of microRNA affects many, many genes-making it that much more difficult for cancer to avoid them and compensate for their loss with an alternative pathway," Satchi-Fainaro concluded. "I hope our findings will apply to other tumor types as a universal approach to treating cancer."
The findings were published in the Jan. 27 issue of ACS Nano.
