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  • Spotlight Review
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Proteasome inhibitors in the treatment of multiple myeloma

Leukemia volume 23, pages 1964–1979 (2009)Cite this article

Abstract

Targeting intracellular protein turnover by inhibiting the ubiquitin–proteasome pathway as a strategy for cancer therapy is a new addition to our chemotherapeutic armamentarium, and has seen its greatest successes against multiple myeloma. The first-in-class proteasome inhibitor, bortezomib, was initially approved for treatment of patients in the relapsed/refractory setting as a single agent, and was recently shown to induce even greater benefits as part of rationally designed combinations that overcome chemoresistance. Modulation of proteasome function is also a rational approach to achieve chemosensitization to other antimyeloma agents, and bortezomib has now been incorporated into the front-line setting. Bortezomib-based induction regimens are able to achieve higher overall response rates and response qualities than was the case with prior standards of care, and unlike these older approaches, maintain efficacy in patients with clinically and molecularly defined high-risk disease. Second-generation proteasome inhibitors with novel properties, such as NPI-0052 and carfilzomib, are entering the clinical arena, and showing evidence of antimyeloma activity. In this spotlight review, we provide an overview of the current state of the art use of bortezomib and other proteasome inhibitors against multiple myeloma, and highlight areas for future study that will further optimize our ability to benefit patients with this disease.

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Acknowledgements

RZO, a Leukemia & Lymphoma Society Foundation Scholar in Clinical Research, would also like to acknowledge support from the Leukemia & Lymphoma Society (6096-07) and the National Cancer Institute (RO1 CA102278).

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  1. Department of Lymphoma & Myeloma, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    J J Shah & R Z Orlowski

  2. Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    R Z Orlowski

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Shah, J., Orlowski, R. Proteasome inhibitors in the treatment of multiple myeloma. Leukemia 23, 1964–1979 (2009). https://doi.org/10.1038/leu.2009.173

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