Proteasome inhibitors for malignancy-related Lambert-Eaton myasthenic syndrome.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder characterized by autoantibodies against presynaptic voltage-gated calcium channels that impair neuromuscular transmission. Malignancies, especially small cell lung cancer (SCLC), have been associated with LEMS and account for approximately 60% of cases, making malignancy management a central step in LEMS therapy. In addition, immunosuppressive therapy is also recommended for symptomatic control. Interestingly, both pathological and epidemiological data suggest that the autoimmune response can inhibit progression of tumors in malignancy-associated LEMS. Thus, conventional broad-spectrum immunosuppressants may not be effective agents for treatment of LEMS, especially in those with malignancy-associated LEMS. Recent preclinical and clinical studies have indicated that proteasome inhibitors can eliminate antibody-producing cells efficiently, block dendritic cell maturation, and have anti-tumor activity. We hypothesize that proteasome inhibitors may be promising agents for treatment of malignancy-related LEMS.
Department of Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; Department of Neurology, Peking Union Medical College Hospital, Beijing, China.
Chen
C
Wang
Shaobo
S
Chen
Bing
B
Feng
Yuzhou
Y
Guan
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D001323:Autoantibodies / Q000276:immunology; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000188:drug therapy* / Q000276:immunology; D061988:Proteasome Inhibitors / Q000627:therapeutic use*
D001323:Autoantibodies; D061988:Proteasome Inhibitors
LEMS; LLPC; SCLC; VGCC; bortezomib; proteasome inhibitor