Proteasome inhibitor-induced gastrointestinal toxicity.
Gastrointestinal toxicities are commonly reported following treatment with proteasome inhibitors. The first-generation proteasome inhibitor, bortezomib, induces significant gastrointestinal side effects including nausea, vomiting, diarrhoea, and constipation, occurring in up to 84% of patients. Despite the development of safer proteasome inhibitors, such as carfilzomib, gastrointestinal toxicities remain some of the most common side effects. This review aims to summarize the previous literature on proteasome inhibitor-induced gastrointestinal toxicities, report on recent updates in the field, and investigate possible mechanisms of this toxicity.



Updates in the literature have included a direct comparison of the safety of approved proteasome inhibitors, bortezomib and carfilzomib, reporting less neurotoxicity and similar gastrointestinal toxicity, from carfilzomib when compared with bortezomib. Many recent studies have investigated the safety of orally bioavailable proteasome inhibitors, such as ixazomib and oprozomib. However, little progress has been made in understanding the possible mechanisms of proteasome inhibitor-induced gastrointestinal toxicities.



Although recent studies have continued to report gastrointestinal toxicities resulting from proteasome inhibitor treatment, particularly when combined with other agents or when administered orally, the mechanisms of proteasome inhibitor-induced gut toxicity remain largely unexplored. Further studies are needed to investigate the pathophysiology of this toxicity to improve the safety of existing and novel proteasome inhibitors.
aAdelaide Medical School, University of Adelaide bDivision of Health Sciences, University of South Australia, Adelaide, Australia.
Romany L
RL
Stansborough
Rachel J
RJ
Gibson
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001896:Boron Compounds / Q000009:adverse effects; D000069286:Bortezomib / Q000009:adverse effects; D002986:Clinical Trials as Topic; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000503:physiopathology; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D009842:Oligopeptides / Q000009:adverse effects; D061988:Proteasome Inhibitors / Q000009:adverse effects*
D000970:Antineoplastic Agents; D001896:Boron Compounds; C554738:ONX 0912; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D000069286:Bortezomib; C548400:ixazomib; C524865:carfilzomib; D005998:Glycine