An analysis of the safety profile of proteasome inhibitors for treating various cancers

Hui Wang, Fangxia Guan, Di Chen, Qing Ping Dou, Huanjie Yang

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Introduction: Emerging evidence demonstrates that the ubiquitin-proteasome pathway is a promising target for cancer therapy. Bortezomib (Velcade) exhibits great efficacy against multiple myeloma (MM) since the first clinical application. However, there are still several limitations associated with the use of bortezomib, including severe toxicities. To overcome bortezomib's shortcomings and to improve its safety profile, several second-generation proteasome inhibitors, for example, carfilzomib, ixazomib, oprozomib and marizomib, have been developed and currently tested in various clinical trials.Areas covered: A literature search was carried out using PubMed and Google Scholar. The activity and safety profiling of proteasome inhibitors in treatment of various cancers were reviewed.Expert opinion: Bortezomib, as a single or in combination therapy, demonstrates efficacy against MM or other hematological malignancies in clinical settings. However, it encounters two major problems, the acquired resistance and the severe side effects. Future direction in bortezomib-based therapy should focus on how to increase or retain its efficacy but improve its safety profile through, for example, rational combination therapies. Second-generation proteasome inhibitors have shown benefits in both overcoming bortezomib resistance and reducing related side effects, although these encouraging results should be further confirmed in a larger clinic population.

Original languageEnglish (US)
Pages (from-to)1043-1054
Number of pages12
JournalExpert Opinion on Drug Safety
Volume13
Issue number8
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Proteasome Inhibitors
Safety
Neoplasms
Multiple Myeloma
Expert Testimony
Hematologic Neoplasms
Proteasome Endopeptidase Complex
Therapeutics
Ubiquitin
Bortezomib
PubMed
Clinical Trials
Population

Keywords

  • Anticancer therapy
  • Clinical trials
  • Proteasome inhibitors
  • Safety profile

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

An analysis of the safety profile of proteasome inhibitors for treating various cancers. / Wang, Hui; Guan, Fangxia; Chen, Di; Dou, Qing Ping; Yang, Huanjie.

In: Expert Opinion on Drug Safety, Vol. 13, No. 8, 2014, p. 1043-1054.

Research output: Contribution to journalReview article

Wang, Hui ; Guan, Fangxia ; Chen, Di ; Dou, Qing Ping ; Yang, Huanjie. / An analysis of the safety profile of proteasome inhibitors for treating various cancers. In: Expert Opinion on Drug Safety. 2014 ; Vol. 13, No. 8. pp. 1043-1054.
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