Navigation Links
Unique dual target specificity of kinase inhibitor key for success against cancer

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 p110á 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 ive. Importantly, dual inhibition of p110á and mTOR with a low dose of PI-103 elicited no drug-related toxicity and was highly effective against human gliomas transplanted into mice.

"These data suggest that combinatorial inhibition of mTOR and p110á represents a safe and effective therapy in the treatment of cancers driven by aberrant signaling through PI3 kinase," says Dr. Weiss. "Glioma represents the most common primary brain tumor, and there are no curative medical therapies. Ultimately, we believe that PI-103 displays the hallmarks of the most successful cancer therapeutics that have been discovered to date as it exhibits a broad action without harmful side effects."


'"/>

Source:Cell Press


Related biology news :

1. Breast Cancer May Be Uniquely Sensitive To Inhibitors Of PI3K Pathway
2. Unique library of plant genes germinates, takes root at UNC
3. Invitrogen Launches i-Path -- A Unique Systems Biology Platform at BIO 2005
4. Uniquely human component of language found in gregarious birds
5. Unique equine cataract surgery offered on routine basis
6. Unique soybean lines hold promise for producing allergy-free soybeans
7. Unique gene regulation gives chilly bugs survival advantage at bottom of the world
8. Unique tomatoes tops in disease-fighting antioxidants
9. New binding target for oncogenic viral protein
10. Ancient olfaction protein is shared by many bugs, offering new pest control target
11. A bacterial genome reveals new targets to combat infectious disease
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/3/2016)... 3, 2016  Neurotechnology, a provider of high-precision ... Automated Biometric Identification System (ABIS) , a complete ... MegaMatcher ABIS can process multiple complex biometric transactions ... of fingerprint, face or iris biometrics. It leverages ... and MegaMatcher Accelerator , which have been ...
(Date:4/26/2016)... BANGALORE, India and LONDON ... Infosys Finacle, part of EdgeVerve Systems, a ... ), and Onegini today announced a partnership to ... banking solutions.      (Logo: http://photos.prnewswire.com/prnh/20151104/283829LOGO ... banks to provide their customers enhanced security to ...
(Date:4/15/2016)... 2016  A new partnership announced today will ... decisions in a fraction of the time it ... high-value life insurance policies to consumers without requiring ... Force Diagnostics, rapid testing (A1C, Cotinine and HIV) ... pressure, weight, pulse, BMI, and activity data) available ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... /PRNewswire/ - FACIT has announced the creation of ... company, Propellon Therapeutics Inc. ("Propellon" or "the Company"), ... portfolio of first-in-class WDR5 inhibitors for the treatment ... represent an exciting class of therapies, possessing the ... cancer patients. Substantial advances have been achieved with ...
(Date:6/23/2016)... 23, 2016 Houston Methodist Willowbrook Hospital ... Sports Association to serve as their official health ... Methodist Willowbrook will provide sponsorship support, athletic training ... association coaches, volunteers, athletes and families. ... Sports Association and to bring Houston Methodist quality ...
(Date:6/23/2016)... June 23, 2016  The Prostate Cancer Foundation (PCF) is pleased ... and faster cures for prostate cancer. Members of the Class of 2016 were ... Read More About the Class of 2016 PCF Young ... ... ...
(Date:6/23/2016)... , June 23, 2016   EpiBiome , ... secured $1 million in debt financing from Silicon Valley ... up automation and to advance its drug development efforts, ... new facility. "SVB has been an incredible ... the services a traditional bank would provide," said Dr. ...
Breaking Biology Technology: