Methods and compositions for identifying, classifying and monitoring subject having Bcl-2 family inhibitor-resistant tumors and cancers

摘要

The invention is directed to methods and kits that allow for identifying, classifying, and monitoring cancer patients for Bcl-2 family inhibitor therapies. The methods and compositions of the invention are directed to determining amplification of Bcl-xL and in cancer or tumor cells, or elevated Bcl-xL polypeptide expression.

主权项

1. A method for identifying a patient with small-cell lung carcinoma or a lymphoma as eligible to receive N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl) piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide therapy or an anti-sense agent designed to bind to one of Bcl-2, Bcl-w, and Bcl-xL comprising:
(a) providing a tissue sample from a patient; (b) determining if expression of a Bcl-xL gene is amplified relative to a baseline control level determined before the administration of N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide; (c) identifying the patient as eligible to receive N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide or the anti-sense agent designed to bind to one of Bcl-2, Bcl-w, and Bcl-xL if the Bcl-xL gene is not amplified; and (d) administering N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide or the anti-sense agent designed to bind to one of Bcl-2, Bcl-w, and Bcl-xL to the patient identified as being eligible to receive N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide or the anti-sense agent designed to bind to one of Bcl-2, Bcl-w, and Bcl-xL.