Narmerguy

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Gfunk6

And to think . . . I hesitated
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This is a well-researched area in Radiation Oncology. Nano-particles with a variety of drugs and isotopes are in clinical development. Haven't heard of RNA conjugates though . . . sounds neat.

Sadly, the main problem here is tumor vasculature. In order for any drug/nanoparticle to reach its target the tumor should be ideally adjacent (or a couple of gap junctions) away from a feeding blood vessel. The bystander effect will probably help but is unlikely to penetrate into severely hypoxic tumor regions.

Also this concept (gene based therapeutics) has been tried many times before using various viral-based vectors, antisense molecules, etc. It sounds elegant in theory but always fails in clinic. I have a special place in my heart for this type of research, but I choose to remain pessimistic for now.
 
Nov 25, 2009
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This is an extremely exciting and promising idea. However, it has a LONG way to go before its clinical utility is proven. This phase I trial out of CalTech had 15 patients. Of the 3 of the patients whose tumors were analyzed, one had a lower level of the target protein (RRM2) than in tumor samples from before treatment. So right now, they've shown that in one patient they were able to decrease the levels of a target protein. Whether this can produce a clinically meaningful response is unclear. Still, it is a very, very exciting early result.

They did show that this system is able to get siRNA into tumor cells without obvious toxicity, and that there was a dose dependent relationship between the dose of nanoparticles administered and the amount they were able to detect in the tumor.

This seems like it could be a promising strategy in combination with radiation for radiosensitization, but I'm a little unclear on the specificity of this targeting system and how effective it would be for distant metastatic disease. It seems that they are relying on the leaky, abnormal blood vasculature of the tumor to allow the 70nm siRNA-containing nanoparticles to enter the tumor cells. Normal blood vessels would prevent the nanoparticles from entering normal tissue in large amounts. Do most micrometastases also have associated leaky blood vessels like the primary tumor? Obviously, some like melanoma and RCC are somewhat known for this, but I'm not sure about breast cancer, for example. Also, aren't many parts of solid tumors poorly vascularized and hypoxic?

I guess the only way to answer these questions is to have more clinical trials.