[Proteasome inhibitors].
BACKGROUND
Proteasome is involved in cell cycle and apoptosis regulation. Its deregulation could participate to oncogenesis.


METHODS
Bortezomib is the first proteasome inhibitor to reach clinical development. Its main adverse events are asthenia, thrombocytopenia and cumulative neurotoxicity which can limits long term use. As single agent, bortezomib displays antitumoral effects in refractory multiple myeloma and mantle cell lymphoma but has only modest activity in solid tumors. Preclinical data suggest that bortezomib could enhance antitumor activity of cytotoxics.


CONCLUSIONS
Proteasome inhibition is a promising therapeutic pathway, especially in lymphoid malignancies.
Alexandre
J
J
Service de médecine interne, unité d'oncologie médicale, groupe hospitalier Cochin-Saint-Vincent-de-Paul, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France. jerome.alexandre@cch.ap-hop-paris.fr
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D005260:Female; D006087:Graft vs Host Reaction; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011480:Protease Inhibitors / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D043823:Taxoids; D000077143:Docetaxel; D000069286:Bortezomib; D003907:Dexamethasone