Abstract
The boronic acid dipeptide bortezomib, able to induce tumor cell death by degradation of key proteins, is the first proteasome inhibitor drug to enter clinical practice. It is employed as first-line treatment in relapsed or resistant multiple myeloma (MM) patients. However, bortezomib often induces a dose-limiting toxicity in the form of painful sensory neuropathy, which can mainly be reduced by subcutaneous administration or dose modification. In this review we focus on the current understanding of the pathophysiological mechanisms of bortezomib-induced neuropathy to allow further studies in animal models and humans, including analysis of clinical and pharmacogenetic aspects, to optimize the treatment regimens.
Highlights
Bortezomib (BTZ), the first successfully proteasome inhibitor used for the treatment of multiple myeloma (MM) and mantle cell patients [1,2], is an antineoplastic drug that reversibly inhibits the mammalian 26S
Toxics 2015, 3 lenalidomide plus low-dose dexamethasone, or in a bortezomib-based triplet regimen such as bortezomib, cyclophosphamide, dexamethasone (VCD), depending on risk level of myeloma patients; eligible patients are treated with an initial BTZ-therapy, followed by autologous hematopoietic stem cell transplantation (AHSCT) [4,5,6,7]
Results obtained from animal models of toxic neuropathies induced by other chemotherapeutic drug suggest that skin biopsy may be a useful tool to examine the correlation between intraepidermal nerve fiber density (IEFN) and chemotherapy-induced peripheral neuropathy, since IEFN degeneration and pain behavior development appear to be linked [38]
Summary
Bortezomib (BTZ), the first successfully proteasome inhibitor used for the treatment of multiple myeloma (MM) and mantle cell patients [1,2], is an antineoplastic drug that reversibly inhibits the mammalian 26S proteasome and interacts with the nuclear factor kappa B (NFκB) system, leading to cytoplasmic aggregate accumulation and cell cycle arrest in cancer cells. BTZ was approved by the US Food and Drug Administration in 2003 as a mono-therapy for progressive MM. Nowadays it is used in induction and consolidation regimens for MM therapy or refractory disease in combination with. Toxics 2015, 3 lenalidomide plus low-dose dexamethasone, or in a bortezomib-based triplet regimen such as bortezomib, cyclophosphamide, dexamethasone (VCD), depending on risk level of myeloma patients; eligible patients are treated with an initial BTZ-therapy, followed by autologous hematopoietic stem cell transplantation (AHSCT) [4,5,6,7]. Little is known about BIPN mechanisms and treatment efficacy, so this review discusses the development of BTZ-induced toxicity in relation to risk factors, the pathophysiological aspects and the management regimes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
