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Background

Lymphangioleiomyomatosis (LAM), the pulmonary manifestation of tuberous sclerosis complex (TSC), is an often fatal disease characterized by the abnormal proliferation of smooth muscle cells, which carry TSC2 gene mutations and which grown aberrantly in the lung, lymph nodes, and peritoneal and plural space. For reasons that are not clearly understood, LAM affects almost exclusively women of reproductive age, suggesting that female hormones might play an important role in promoting LAM pathogenesis.

Currently, there is no approved drug for the treatment or prophylaxis of LAM, and new therapies and preventatives are clearly needed for treating LAM and related pathologies of this disease.

Description

Dr. Elizabeth Petri-Henske and Dr. Jane Yu have discovered a new treatment and method of prophylaxis for LAM in mammals, and they have created a novel animal model useful in the development of potential target therapies for LAM and other estrogen-mediated malignancies.

They have found that estrogen induces the dissemination of tumor cells, increases the number of circulating tumor cells, and enhances lung colonization. As a result, the two investigators have hypothesized several therapeutic treatments against LAM, including using an inhibitor of the MEK-1 and MEK-2 kinases. Further in-vivo experiments have proved that this inhibitor delays the development of primary tumors and blocks estrogen-induced lung metastases.

Publications

• Yu, J.J. et al., "Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells," Proc Natl Acad Sci U S A. (2009); 106(8): 2635-40
• Hartman, T.R. et al., "The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway," Hum Mol Genet. (2009); 18(1) :151-63

Patent Status:

• U.S. Patent Application pending

For licensing information, contact

Clarissa Ceruti, PhD, MBA
Associate Director
Office of Corporate Alliances
Fox Chase Cancer Center
610 Old York Road, Room 407
Jenkintown, PA 19046
Tel.: 215-214-1546
Fax: 215-214-1440
clarissa.ceruti@fccc.edu