Sphingosine-1-Phosphate Lyase Polypeptides, Polynucleotides and Modulating Agents and Methods of Use

Case Number CH-009, CH-029

Inventors: Julie Saba, MD, PhD, et al.

Patent No Title Issue Date Country
Patent No Title Issue Date Country
6,423,527 Sphingosine-1-Phosphate Lyase Polypeptides, Polynucleotides and Modulating Agents and Methods of Use 7/23/2002 United States
Pending     PCT
Pending     Japan
Pending     Hong Kong
Pending     Canada
Pending     European
6,569,666   5/27/2003 United States
6,495,359   12/17/2002 United States
6,830,881 B2   12/4/2004 United States
Pending     United States
Pending     United States
Pending     United States
CH-029      
Pending Compounds and Methods for the Modulation of Sphingolipid Metabolism   United States
Pending     Hong Kong
Pending     United States
Pending     European
Pending     PCT
Pending     Canada
Pending     Japan
Pending     United States

Abstract
These inventions provide novel compositions, methods and kits for the diagnosis and treatment of cancers, such as breast and colon cancer, through the use of sphingosine-1-phosphate lyase (SPL) polynucleotides and polypeptides, and agents that modulate the expression and activity of such polypeptides.

Sphingosine-1-phosphate (S-1-P), an endogenous phosphorylated long chain base (LCBP), has been shown to regulate both the growth and invasiveness of human cancer cells. S-1-P also plays a role in endothelial cell function, angiogenesis and platelet function. The actions of S-1-P are mediated in part via stimulation of a specific signal transduction pathway by binding to a specific G protein coupled receptor. S-1-P also functions as an intracellular lipid second messenger in a receptor-independent fashion. The genes and gene products required for S-1-P metabolism and signaling may, therefore, provide novel molecular targets for the treatment of cancer, among other diseases.

Advantage
The course of treatment for a particular breast cancer is often selected based on a variety of prognostic parameters, including an analysis of specific tumor markers. However, the use of established markers often leads to a result that is difficult to interpret. Further, current therapies are inadequate for inhibiting tumor invasiveness and metastasis.

This invention provides compositions and methods that modulate SPL activity with a pharmaceutically acceptable carrier, inhibiting the ability of an endogenous SPL to degrade S-1-P. Kits for detecting SPL and for detecting an alteration in the S-1-P gene enable and facilitate diagnosis and treatment of cancer may be developed.

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