The researchers developed a nanoparticle carrying a molecular marker that binds to the surface of cancer cells, triggering the cells to absorb it. The siRNA carried within the particle was designed to silence a gene called ribonucleotide reductase M2 (RRM2), which regulates DNA synthesis and repair and is known to be an anticancer target. Because it was the first trial using targeted RNAi delivery for cancer, says Mark Davis, a professor of chemical engineering at Caltech and the study’s lead author, “we wanted to choose a gene that was suspected to be hugely upregulated in a broad spectrum of cancers” in order to increase the likelihood of being able to observe the novel therapy’s effect.
The researchers analyzed biopsy samples from three melanoma patients in the trial who had received different doses of the therapy. They tracked the particles in the different samples, finding that the amounts they could see in the tumor cells correlated with the doses the patients received. “That’s the first time anyone has seen that for any kind of particle delivery system, whether it’s a liposome, a nanoparticle, or anything,” says Davis. They also pulled out samples of mRNA cleaved exactly where the siRNA’s were designed to cut, showing that the RNAi did its job the way it was expected to. The study does not discuss the clinical effects of the treatment on the melanoma patients in the trial; that data, says Davis, will be presented at the meeting of the American Society of Clinical Oncology in early June.
As I was reading this, I kept thinking: yep, that’s all very nice, but does it actually shrink the tumors or help the patients live longer? And lo and behold, the next paragraph would bring up just that question.