Interleukin-6 as a Therapeutic Target - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Clinical Cancer Research Année : 2015

Interleukin-6 as a Therapeutic Target

Résumé

Human IL6 is a cytokine produced by many cell types that has pleiotropic effects. In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Blocking IL6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory diseases (rheumatoid arthritis) without major toxicity. Interestingly, the inhibition of C-reactive protein (CRP) production is a trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R mAb. In various cancers, in particular plasma cell cancers, large randomized trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP production in treated patients in vivo, the numerous data showing an involvement of IL6 in these diseases, and initial short-term treatments demonstrating a dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is the plasticity of cancer cells, with the presence of various subclones, making the outgrowth of cancer subclones possible using growth factors other than IL6. In addition, current therapeutic strategies used in these cancers already target IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production in vivo and are safe and useful in inflammatory diseases and Castleman disease.

Domaines

Cancer

Dates et versions

hal-02137928 , version 1 (23-05-2019)

Identifiants

Citer

Jean-François Rossi, Zhao-Yang Lu, Michel Jourdan, Bernard Klein. Interleukin-6 as a Therapeutic Target. Clinical Cancer Research, 2015, 21 (6), pp.1248-1257. ⟨10.1158/1078-0432.CCR-14-2291⟩. ⟨hal-02137928⟩
38 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More