{"entity":{"id":"proteasome-inhibitor","kind":"term","name":"Proteasome inhibitor (bortezomib, carfilzomib, ixazomib)","aka":["proteasome inhibitors","proteasome inhibition","PI-based"],"tldr":"Drugs that block the cell's protein-recycling machine. Myeloma cells make huge amounts of antibody protein and choke on the backlog when the proteasome is blocked; normal cells cope far better.","summary":"Bortezomib (2003) was the first, given subcutaneously to limit neuropathy; carfilzomib is irreversible and more potent but has cardiovascular toxicity; ixazomib is oral. They pair with immunomodulatory drugs and dexamethasone in VRd/KRd induction, in relapsed combinations with daratumumab or isatuximab, and bortezomib is also used in mantle cell lymphoma and AL amyloidosis. Resistance and the shift to CD38 antibodies, CAR-T and bispecifics have reduced their role at relapse, but they remain in nearly every first-line regimen.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Proteasome_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proteasome_inhibitor"}],"tags":[],"related":["vrd","imid","peripheral-neuropathy"],"cancers":["multiple-myeloma"],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["bortezomib","ixazomib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},"route":"/terms/proteasome-inhibitor/","neighbours":{"term":[{"id":"imid","kind":"term","name":"Immunomodulatory drugs (IMiDs) and CELMoDs","route":"/terms/imid/"},{"id":"peripheral-neuropathy","kind":"term","name":"Peripheral neuropathy (chemotherapy-induced)","route":"/terms/peripheral-neuropathy/"},{"id":"vrd","kind":"term","name":"VRd and Dara-VRd (myeloma induction regimens)","route":"/terms/vrd/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-transplant-eligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-eligible","route":"/cancers/myeloma-transplant-eligible/"},{"id":"myeloma-transplant-ineligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-ineligible","route":"/cancers/myeloma-transplant-ineligible/"},{"id":"plasma-cell-leukaemia","kind":"cancer","name":"Plasma cell leukaemia","route":"/cancers/plasma-cell-leukaemia/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"drug":[{"id":"bortezomib","kind":"drug","name":"Bortezomib","route":"/drugs/bortezomib/"},{"id":"ixazomib","kind":"drug","name":"Ixazomib","route":"/drugs/ixazomib/"}]}}