Cancer therapies and methods

A method for identifying a cancer patient for whom administration of an inhibitor of the ubiquitin-proteasome system would be therapeutically beneficial, the method comprising:

• a. determining whether the cancer present in a patient is associated with cells in which the functional activity of SMARCB1 is low or absent;
• b. where the cancer is found in step (a) to be associated with cells in which the functional activity of SMARCB1 is low or absent, identifying the patient as a cancer patient for whom administration of an inhibitor of the ubiquitin-proteasome system would be therapeutically beneficial;
• and
• c. administering an inhibitor of the ubiquitin-proteasome system to said patient,
• wherein the cancer is selected from the group consisting of malignant rhabdoid tumors, atypical teratoid/rhabdoid tumors, epithelioid sarcomas, synovial sarcomas, undifferentiated sarcomas with or without rhabdoid features, extraskeletal myxoid chondrosarcomas, schwannomas, familial and sporadic schwannomatosis, cribriform neuroepithelial tumours, choroid plexus carcinomas, teratomas, primitive neuroectodermal tumours, and myoepithelial carcinomas.

A method for determining whether a cancer patient will therapeutically benefit or at least likely will benefit from the administration of an inhibitor of the ubiquitin-proteasome system:

• a. determining whether the cancer present in a patient is associated with cells in which the functional activity of SMARCB1 is low or absent or likely to be low or absent;
• b. where the cancer is found in step (a) to be associated with cells in which the functional activity of SMARCB1 is low or absent or likely to be low or absent, identifying the patient as a cancer patient for whom administration of an inhibitor of the ubiquitin-proteasome system will be or will likely be therapeutically beneficial, and administering an inhibitor of the ubiquitin-proteasome system to said patient;
• and
• where the cancer is found in step (a) to be associated with cells in which the functional activity of SMARCB1 is present and the level is not significantly lower than the level in a normal control, identifying the patient as a cancer patient for whom administration of an inhibitor of the ubiquitin-proteasome system is likely not to be therapeutically beneficial,
• wherein the cancer is selected from the group consisting of malignant rhabdoid tumors, atypical teratoid/rhabdoid tumors, epithelioid sarcomas, synovial sarcomas, undifferentiated sarcomas with or without rhabdoid features, extraskeletal myxoid chondrosarcomas, schwannomas, familial and sporadic schwannomatosis, cribriform neuroepithelial tumours, choroid plexus carcinomas, teratomas, primitive neuroectodermal tumours, and myoepithelial carcinomas.

A method for treating cancer in a patient, the method comprising:

• a. determining whether the cancer present in a patient is associated with cells in which the functional activity of SMARCB1 is low or absent;
• and
• b. where the cancer is found in step (a) to be associated with cells in which the functional activity of SMARCB1 is low or absent, administering to the patient an amount of an inhibitor of the ubiquitin-proteasome system that is effective to treat said cancer,
• wherein said cancer is selected from the group consisting of malignant rhabdoid tumors, atypical teratoid/rhabdoid tumors, epithelioid sarcomas, synovial sarcomas, undifferentiated sarcomas with or without rhabdoid features, extraskeletal myxoid chondrosarcomas, schwannomas, familial and sporadic schwannomatosis, cribriform neuroepithelial tumours, choroid plexus carcinomas, teratomas, primitive neuroectodermal tumours, and myoepithelial carcinomas.