LGND presents at many conferences and some slip through the cracks (they just presented at ASCO and the ADA meeting and will soon be at the International AIDS meeting in Stockholm.
The experiment isn't that unexpected, but the result was quite striking. Here's the abstract of the earlier paper which led to the current results (to be published in another paper):
Cancer Res 1998 Feb 1;58(3):479-484
Beyond tamoxifen: the retinoid X receptor-selective ligand LGD1069
(TARGRETIN) causes complete regression of mammary carcinoma.
Bischoff ED, Gottardis MM, Moon TE, Heyman RA, Lamph WW
Department of Retinoid Research, Ligand Pharmaceuticals, Inc., San Diego, California 92121, USA.
Recently, we reported that LGD1069, a high-affinity ligand for the retinoid X receptors (RXRs), was shown to have an efficacy
equivalent to that of tamoxifen (TAM) as a chemopreventive agent in the N-nitroso-N-methylurea-induced rat mammary
carcinoma model. Furthermore, LGD1069 was very well tolerated during 13 weeks of chronic therapy with no classic signs of
"retinoid-associated" toxicities. Due to the high efficacy and benign profile of this RXR agonist as a suppressor of carcinogenesis,
we examined its role as a therapeutic agent on established mammary carcinomas. In the rat mammary carcinoma model,
N-nitroso-N-methylurea was used to induce tumors, and the tumors were allowed to grow to an established size prior to initiation
of treatment. LGD1069-treated animals showed complete regression in 72% of treated tumors and had a reduced tumor load
compared to control. In addition, the combination of LGD1069 and TAM showed increased efficacy over either agent alone.
Histopathological analysis showed a reduction of LGD1069-treated tumor malignancy, an increase in differentiation, and a sharp
decrease in cellular proliferation compared to vehicle-treated control tumors. These data demonstrate that the RXR-selective
ligand LGD1069 is a highly efficacious therapeutic agent for mammary carcinoma and enhances the activity of TAM.
PMID: 9458093, UI: 98117297 |
