Compositions and methods for inhibiting growth of...

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A61K 39/395 (2006.01) A61K 38/18 (2006.01) A61K 38/45 (2006.01) A61K 45/00 (2006.01) A61K 47/48 (2006.01) A61K 49/00 (2006.01) A61K 51/10 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2662905

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.v.beta.6, and the responsiveness of patient populations to .alpha.v.beta.6-active compounds and compositions (e.g., antibodies and other ligands that bind .alpha.v.beta.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.v.beta.6-active compounds and compositions by examining the expression of .alpha.v.beta.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.v.beta.6 on the surfaces of tumor cells and/or that block one or more components of the TGF-.beta. pathway, particularly in 5/<=.alpha.rf4-deficient tumor cells.

La présente invention relève du domaine de la biologie cellulaire, de l'immunologie et de l'oncologie et repose sur la découverte de l'existence d'un rapport entre les niveaux d'expression du gène suppresseur de tumeur smad4 (également appelé dpc4) et de l'intégrine .alpha.v.beta.6 et la réponse de populations de patients à des composés et compositions actifs en .alpha.v.beta.6 (tels que des anticorps et autres ligands liant .alpha.v.beta.6), en particulier dans des cellules cancéreuses issues de telles populations de patients, plus particulièrement sur des carcinomes tels que des carcinomes pancréatiques. Cette invention concerne ainsi des méthodes permettant de déterminer la réponse de cellules tumorales (en particulier de cellules de tumeurs pancréatiques) à ces composés et compositions actifs en .alpha.v.beta.6 en examinant l'expression de .alpha.v.beta.6 et de smad4 par les cellules tumorales, ainsi que des méthodes de diagnostic et de traitement/prévention de la progression de tumeurs utilisant des ligands, y compris des anticorps et des médicaments à petites molécules, qui se lient à l'intégrine .alpha.v.beta.6sur les surfaces de cellules tumorales et/ou qui bloquent un ou plusieurs composants de la voie TGF-.beta.,en particulier dans des cellules de tumeurs à déficience en smad4.

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