Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy

Genomic alterations may make cancer cells more dependent than normal cells on mechanisms of proteostasis, including protein folding and degradation. This proposition is the basis for the clinical use of proteasome inhibitors to treat multiple myeloma and mantle cell lymphoma. However, proteasome inhibitors have not proved effective in treating other cancers, and this has called into question the general applicability of this approach. Here, I consider possible explanations for this apparently limited applicability, and discuss whether inhibiting other broadly acting components of the ubiquitin-proteasome system - including ubiquitin-activating enzyme and the AAA-ATPase p97/VCP - might be more generally effective in cancer therapy.

• Publication year

  2014

• Venue

  BMC Biology

• Publication date

  2014-11-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s12915-014-0094-0PMID 25385277PMCID 4226866
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Holland-Frei Cancer Medicine

  2016cited by this paper
• Panorama 1: A randomized, double-blind, phase 3 study of panobinostat or placebo plus bortezomib and dexamethasone in relapsed or relapsed and refractory multiple myeloma.

  2014cited by this paper
• Proteasome-mediated processing of Nrf1 is essential for coordinate induction of all proteasome subunits and p97.

  2014cited by this paper
• Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy.

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• Create and preserve: proteostasis in development and aging is governed by Cdc48/p97/VCP.

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  2014cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2013influential reference
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  2013cited by this paper
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  2013influential reference
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  2012cited by this paper
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  2012influential reference
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  2012cited by this paper
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  2011cited by this paper
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  2010cited by this paper
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