TY - JOUR
T1 - An analysis of the safety profile of proteasome inhibitors for treating various cancers
AU - Wang, Hui
AU - Guan, Fangxia
AU - Chen, Di
AU - Dou, Qing Ping
AU - Yang, Huanjie
N1 - Funding Information:
manuscript. Grant support: This work was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLXS011 to H Yang), NCI R01 CA127258 and POPII-Canadian Institutes of Health Research FRN 120216 Sub-Contract from McGill (Q.P. Dou) and Scientific and Technological Research Project of Henan Province, China, # 1221023 10542 (F. Guan & D. Chen).
Funding Information:
This work was supported by the Scientific Research Foundation of Harbin Institute of Technology, the Innovation Research Project of Harbin, the National Cancer Institute, the Canadian Institute of Health Research and the Scientific Technological Research Project of Henan Province, China. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Anticancer therapy
KW - Clinical trials
KW - Proteasome inhibitors
KW - Safety profile
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U2 - 10.1517/14740338.2014.939953
DO - 10.1517/14740338.2014.939953
M3 - Review article
C2 - 25005844
AN - SCOPUS:84904462472
SN - 1474-0338
VL - 13
SP - 1043
EP - 1054
JO - Expert Opinion on Drug Safety
JF - Expert Opinion on Drug Safety
IS - 8
ER -