Compositions and Methods for the Modulation of Sphingolipid Metabolism and/or Signaling

Technology Number: CH-009

 

IP Status: Patent issued, available for exclusive field of use or non-exclusive licensing

 

Inventor: Dr. Julie D. Saba and Dr. Henrik Fyrst

 

Background: Breast cancer is the most common form of cancer and remains the second leading cause of cancer death in American women, despite advances in both detection and treatment. There is no single effective prevention or treatment method for breast cancer management, which currently relies on both early detection diagnosis and aggressive treatment, including chemotherapy, radiation, and surgery. The specific treatment chosen is based on a variety of prognostic tests, including analysis of specific molecular tumor markers, but such tests often lead to unclear results. An important criteria for predicting recovery of breast cancer patients is tumor invasiveness and metastasis: for example, the five-year survival rate for localized breast cancer is 90%, but falls below 20% once the cancer metastasizes.

 

Invention Description: The present invention relates to methods for diagnosis and therapy of cancer through modulation of Sphingosine-1-Phosphate Lyase (SPL) activity. This method provides for a nucleotide sequence encoding polypeptides having SPL activity, as well as the preparation of SPL through growth in a host cell. This method further allows one to identify agents that modulate SPL activity by presenting cells containing SPL activity with a potential agent and measuring SPL or SPL mRNA levels before and after. A comparison yielding significant changes in expression points to SPL activity modulation. In addition, this method provides for a pharmaceutical composition that contains the SPL modulating agent, preferably by enzyme inhibition to subsequently inhibit growth of breast cancer cells and present further development and/or metastasis of breast cancer cells. This method also reveals diagnostic and prognostic techniques for breast cancer by way of detection and evaluation of SPL gene alteration in breast tissue biopsy samples.

 

Application(s): This method is based on the discovery that Sphingosine-1-Phosphate (S1P) acts as a tumor suppressor lipid to inhibit breast cancer cell growth while not affecting non-tumor cells. Targeting and inhibiting SPL, which catalyzes cleavage of S1P, increase S1P concentration in the cells, thereby preventing cancer cell growth for use as a potential cancer therapy.

 

Advantages: This method provides a novel approach to the treatment and diagnosis of breast cancer in that it works to rid the body of cancer cells without affecting any of the normal somatic cells, which under current therapies tend to lead to the severe side effects patients experience while undergoing cancer treatment.

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