@entity1582 is a plasma cell malignancy with an estimated 26,850 new cases and 11,240 deaths in 2015 in the United States. Two main classes of agents are the mainstays of therapy-proteasome inhibitors (PI) and immunomodulatory drugs (IMiD). Other new targets are emerging rapidly, including monoclonal antibodies and histone deacetylase (HDAC) inhibitors. These therapeutic options have greatly improved overall survival, but currently only 15% to 20% of @entity1 experience long-term progression-free survival or are cured. Therefore, improvement in treatment options is needed. One potential means of improving clinical options is to target resistance mechanisms for current agents. For example, eliminating the cytoprotective heat-shock response that protects @entity1582 cells from proteasome inhibition may enhance PI-based therapies. The transcription factor @entity22585 ( @entity22585 ) is the master regulator of the heat-shock response. @entity22585 is vital in the proteotoxic stress response, and its activation is controlled by posttranslational modifications (PTM). This review details the mechanisms of @entity22585 regulation and discusses leveraging that regulation to enhance PI activity.

When Cancer Fights Back: Multiple XXXX , Proteasome Inhibition, and the Heat-Shock Response.

@entity1582 :: ('MESH:D009101', 'Disease') :: ['myeloma', 'Multiple myeloma'] @entity1 :: ('9606', 'Species') :: ['patients'] @entity22585 :: ('3297', 'Gene') :: ['HSF1', 'heat-shock factor 1']
@entity1582 :: (MESH:D009101,Disease) :: ['Myeloma']
