Scientists have identified a new molecule that inhibits proliferation of a broad range of lethal malignant glioma cells in vitro and in vivo. The findings, published in the May issue of Cancer Cell, shed light on which PI3 kinase family members are most likely to play a role in cancer progression. This study reinforces the concept that successful small molecule kinase inhibitors must display a broad reactivity to effectively attenuate the complex signaling pathways involved in malignant transformation and to thwart to the ability of cancer cells to adapt to stress.

Lipid kinases belonging to the PI3 kinase family, made up of different isoforms, promote cell growth and survival. Aberrant regulation and activation of PI3 kinases has been implicated in several human malignancies. Although the specific mechanisms and PI3K-associated molecules involved in cancer are not clear, this kinase family represents a rational and promising target for design of new cancer therapeutics. Dr. William A. Weiss, from the Department of Neurology at the University of California, San Francisco and coworkers sought to identify which PI3 kinase isoforms are critical for growth and progression of malignant glioma cells. UCSF colleagues Zachary Knight and Kevan Shokat synthesized and characterized a series of novel inhibitors that span the different PI3 kinase isoforms (described in the May issue of Cell). Qi-Wen Fan in the Weiss lab screened these agents in glioma cell lines. One compound, PI-103, uniquely and potently blocked the growth of glioma cells.

The cellular activity of PI-103 was traced to its ability to cooperatively inhibit both the p110 subunit of PI3 kinase and a downstream molecule called mTOR that also plays a critical role in cell growth. Although both of these molecules are members of the same signaling cascade, the researchers found that they must be concurrently inhibited because of a regulatory feedback loop that renders a monospecific inhibitor ineffect
'"/>

Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
15-May-2006

Page: 1 2
Related biology news :

1. Unique tomatoes tops in disease-fighting antioxidants
2. Unique estrogen receptor linked to metastatic breast cancer
3. Unique imaging uncovers the invisible world where surfaces meet
4. Unique gene regulation gives chilly bugs survival advantage at bottom of the world
5. Unique Huntingtons study moves forward
6. Unique soybean lines hold promise for producing allergy-free soybeans
7. Uniquely human component of language found in gregarious birds
8. Unique equine cataract surgery offered on routine basis
9. Unique interplay between tumor and blood vessel cells promotes angiogenesis and tumor growth
10. Unique genetic profile helps over-45s conceive naturally
11. Unique library of plant genes germinates, takes root at UNC