Compositions and methods for inhibiting growth of smad4-deficient cancers
The present invention is in the fields of cell biology, immunology and oncology. The invention relates to the discovery that there is a relationship between the expression levels of the tumor suppressor gene smad4 (also known as dpc4) and integrin .alpha..sub.v.beta..sub.6, and the responsiveness of patient populations to .alpha..sub.v.beta..sub.6-active compounds and compositions (e.g., antibodies and other ligands that bind .alpha..sub.v.beta..sub.6), particularly in cancer cells from such patient populations, more particularly on carcinomas such as pancreatic carcinomas. The invention thus provides methods for determining the responsiveness of tumor cells (particularly those from pancreatic tumors) to such .alpha..sub.v.beta..sub.6-active compounds and compositions by examining the expression of .alpha..sub.v.beta..sub.6 and smad4 by the tumor cells, as well as methods of diagnosis and treatment/prevention of tumor progression using ligands, including antibodies and small molecule drugs, that bind to integrin .alpha..sub.v.beta..sub.6 on the surfaces of tumor cells and/or that block one or more components of the TGF-.beta. pathway, particularly in smad4-deficient tumor cells.
Violette; Shelia M. (Lexington, MA), Koopman; Louise A. (Brookline, MA)
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