Abstract: Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers associated with the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.

Abstract: Disclosed are methods for the treatment of various solid tumors in patients in need of such treatment. The methods comprise administering to such a patient an NEDD8-activating enzyme (NAE) inhibitor such as ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]-pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate (MLN4924) or a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents. Also disclosed are medicaments for use in the treatment of various solid tumors.

Abstract: Disclosed are methods for the treatment of various solid tumors in patients in need of such treatment. The methods comprise administering to such a patient an NEDD8-activating enzyme (NAE) inhibitor such as ((1S,2S,4R)-4-(4-((1S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]-pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate (MLN4924) or a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents. Also disclosed are medicaments for use in the treatment of various solid tumors.

Abstract: Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers associated with the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.

Abstract: Disclosed are methods for the treatment of various solid tumors in patients in need of such treatment. The methods comprise administering to such a patient an NEDD8-activating enzyme (NAE) inhibitor such as (1S,2S,4R)-4-4-(1S)-2,3-dihydro 1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]-pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate (MLN4924) or a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents. Also disclosed are medicaments for use in the treatment of various solid tumors.

Abstract: The present invention relates to methods for the diagnosis and treatment of a cancer or cancer. Specifically, the present invention identifies the differential expression of 15986, 2188, 20743, 9148, 9151, 9791, 44252, 14184, 42461, 8204, 7970, 25552, 21657, 26492, 2411, 15088, 1905, 28899, 63380, 33935, 10480, 12686, 25501, 17694, 15701, 53062, 49908, 21612, 38949, 6216, 46863, 9235, 2201, 6985, 9883, 12238, 18057, 21617, 39228, 49928, 54476, 62113, 64316, 12264, 32362, 58198, 2887, 3205, 8557, 9600, 9693, 44867, 53058, 55556, 57658, 2208, 10252, 10302, 14218, 33877, 10317, 10485, 25964, 14815, 1363, 1397, 14827, 21708, 3801, 64698, 2179 and 13249 genes in tissues relating to cancer, relative to their expression in normal, or non-cancer disease states, and/or in response to manipulations relevant to a cancer. The present invention describes methods for the diagnostic evaluation and prognosis of various cancers, and for the identification of subjects exhibiting a predisposition to such conditions.

Abstract: The invention relates to methods for measuring proteasome activity in biological samples. More particularly, then invention relates to methods for monitoring drug action following in vivo administration of a proteasome inhibitor. The invention provides methods and kits for monitoring pharmacodynamic drug action and for determining dose regimen for a proteasome inhibitor. The invention also provides methods for determining baseline proteasome activity in a mammal.

Abstract: The present invention relates to methods for the diagnosis and treatment of a cancer or cancer. Specifically, the present invention identifies the differential expression of 140, 1470, 1686, 2089, 2427, 3702, 5891, 6428, 7181, 7660, 25641, 69583, 49863, 8897, 1682, 17667, 9235, 3703, 14171, 10359, 1660, 1450, 18894, 2088, 32427, 2160, 9252, 9389, 1642, 85269, 10297, 1584, 9525, 14124, 4469, 8990, 2100, 9288, 64698, 10480, 20893, 33230, 1586, 9943, 16334, 68862, 9011, 14031, 6178, 21225, 1420, 32236, 2099, 2150, 26583, 2784, 8941, 9811, 27444, 50566 and 66428 genes in tissues relating to cancer, relative to their expression in normal, or non-cancer disease states, and/or in response to manipulations relevant to a cancer. The present invention describes methods for the diagnostic evaluation and prognosis of various cancers, and for the identification of subjects exhibiting a predisposition to such conditions.