Here's the abstractfor the other retinoid paper:
Novel retinoid-related molecules as apoptosis inducers and effective inhibitors of human
lung cancer cells in vivo
Xian-Ping Lu1, Andrea Fanjul1?3, Nathalie Picard1, Michaela Pfahl1, Deepa Rungta1, Karen
Nared-Hood1, Bruce Carter3, Javier Piedrafita2, Shiping Tang2, Eric Fabbrizio2 & Magnus Pfahl1?3
1Galderma Research, Inc., 3099 Science Park Road, Suite 250, San Diego, California 92121,
USA, 2Sidney Kimmel Cancer Center, 3099 Science Park Road, Suite 200, San Diego,
California 92121, USA, 3Maxia Pharmaceuticals, Inc., 3099 Science Park Road, Suite 250,
San Diego, California 92121 USA, Correspondence should be addressed to Magnus Pfahl.
Lung cancer causes more than 140,000 deaths annually in the United States
alone, and the prognosis for non-small cell lung cancer (NSCLC) is particularly
poor1. Therapies using small molecules that preferentially kill lung tumor cells
by inducing cellular suicide (apoptosis) would therefore be highly desirable.
Retinoids have shown promise as cancer preventive and cancer therapeutic
agents2?5. Retinoid signals are mediated by two classes of nuclear receptors:
the retinoic acid receptors (RAR*, á, and *) and the retinoid X receptors
(RXR*, á and *)5?8. These receptors usually bind as heterodimers to specific
DNA sequences9 and/or interact with other transcriptional regulators, such as
AP-1 (ref. 10) to regulate gene transcription. Synthetic retinoids can be made
that activate only specific portions of the complex retinoid response
network11?15 and activate selective biological programs. To identify retinoids
with novel biological activities, we used a high-throughput "biological activity
fingerprint" screen on a large library of retinoids and retinoid-related
molecules (RRMs). We identified new structures that are highly effective
against lung cancer cells in vitro, inducing apoptosis. We show here for one of
these compounds that it is very effective against a human NSCLC in vivo in an
animal model. These new molecules show a distinct pattern of receptor
signaling. |
