I've looked at the PNU rat model some more. It has been shown to demonstrate chemoprevention by Tamoxifen, Raloxifene, Panretin, and Targretin. Retinoids, such as tretinoin (ATRA, the active ingredient in Reton-A, Renova, and Vessinoid) and iso-tretinoin (13-cis retinoic acid, the active ingredient in Accutane) have not produce very robust chemoprevention data in the model.
The model's strength comes from the fact that the breast tumors develop from the carcinogen. They go through the various stages of tumor development and frequently different tumors show up at different times. LGND looked at the effect of Targretin on the primary tumor (reaching 75 cm within 4 days of initiating treatment), as well as the secondary tumors (tumors that reached that size subsequently). For complete regression of primaries, Targretin beat Tamoxifen 72% to 33%. After 6 weeks Targretin produced complete regression of all tumors (primary and secondary) in 46% of the treated animals, while Tamoxifen achieved such a result in 20%. In fact, Targretin did just about twice as good as Tamoxifen in virtually every parameter measured.
This is significant, because Tamoxifen is the hormonal treatment of choice for human breast cancer. It clearly also works in this rat model, but Targretin works twice as well. Of course at this time the paper does not have a definitive reason on why Targretin did so well. Several clinical trials were proposed as well as several molecular mechanisms. We will learn more soon, but it's clear that thus far, the results are stunning. |
