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Author Notes:

Correspondence: Lawrence H. Boise Department of Hematology and Medical Oncology Winship Cancer Institute of Emory University Emory University School of Medicine 1365 Clifton Road NE Room C4012 Atlanta, GA 30322 404-778-4724 ; Email: lboise@emory.edu

We thank Faith E. Davies for her thoughtful feedback.

Disclosures: Lonial: Consultancy - Millennium: The Takeda Oncology Company, Celgene, Novartis, Bristol-Myers Squibb, Onyx Pharmaceuticals, Janssen Pharmaceutical Companies: The Pharmaceutical Companies of Johnson & Johnson

Subjects:

Research Funding:

Support provided by P30 CA138292 and The TJ Martell Foundation.

LHB is a Georgia Cancer Coalition Distinguished Cancer Scientist.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Cell Biology
  • UNFOLDED PROTEIN RESPONSE
  • TRANSCRIPTION FACTOR HSF1
  • NF-KAPPA-B
  • HSP90 INHIBITOR
  • GENE-EXPRESSION
  • CELL-LINES
  • FACTOR-I
  • MOLECULAR-MECHANISMS
  • ANTICANCER STRATEGY
  • PROTEOTOXIC STRESS

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

Tools:

Journal Title:

Molecular Cancer Research

Volume:

Volume 13, Number 8

Publisher:

, Pages 1163-1173

Type of Work:

Article | Final Publisher PDF

Abstract:

Multiple myeloma 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 patients 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 myeloma cells from proteasome inhibition may enhance PI-based therapies. The transcription factor heatshock factor 1 (HSF1) is the master regulator of the heat-shock response. HSF1 is vital in the proteotoxic stress response, and its activation is controlled by posttranslational modifications (PTM). This review details the mechanisms of HSF1 regulation and discusses leveraging that regulation to enhance PI activity.

Copyright information:

© 2015 American Association for Cancer Research.

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