Cancer relapse under chemotherapy: Why TLR2/4 receptor agonists can help

被引:96
作者
Garay, Ricardo P.
Viens, Patrice
Bauer, Jacques
Normier, Gerard
Bardou, Marc
Jeannin, Jean-Francois
Chiavaroli, Carlo
机构
[1] Univ Paris 07, EA2381, Paris, France
[2] Univ Mediterranee, Inst J Paoli I Calmettes, UMR 599, Marseille, France
[3] OM Pharma, Meyrin, Switzerland
[4] Univ Bourgogne, Dept Med, Unite Pharmacol Clin, Fac Med Dijon, Dijon, France
[5] Univ Bourgogne, EPHE, INSERM, Lab Immunol & Immunotherapie Canc,Unit 517, Dijon, France
[6] Univ Bourgogne, IFR 100, Dijon, France
关键词
Toll-like receptor; TLR agonist; TNF; OM-174; chemotherapy;
D O I
10.1016/j.ejphar.2007.02.018
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Liver or lung metastases usually relapse under chemotherapy. Such life-threatening condition urgently needs new, systemic anticancer compounds, with original and efficient mechanisms of action. In B16 melanoma mice treated with cyclophosphamide, D'Agostim et al. [D'Agostini, C., Pica, F., Febbraro, G., Grelli, S., Chiavaroli, C., Garaci, E., 2005. Antitumour effect of OM-174 and Cyclophosphamide on murine B16 melanoma in different experimental conditions. Int. Immunopharniacol. 5, 1205-1212.] recently found that OM-174, a chemically defined Toll-like receptor(TIR)2/4 agonist, reduces tumor progression and prolongs survival. Here we review 149 articles concerning molecular mechanisms of TLR2/4 agonists, alone or in combination with chemotherapy. It appears that TLR2/4 agonists induce a well controlled tumor necrosis factor-alpha (TNF-alpha) secretion, at plasma levels known to permeabilize neoangiogenic tumor vessels to the passage of cytotoxic drugs. Moreover, TLR2/4 agonists induce inducible nitric oxide synthase (NOS) expression, and nitric oxide is able to induce apoptosis of chemotherapy-resistant tumor cell clones. Finally, TLR2/4-stimulation activates dendritic cell traffic and its associated tumor-specific, cytotoxic T-cell responses. Therefore, parenteral TLR2/4 agonists seem promising molecules to prolong survival in cancer patients who relapse under chemotherapy. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 17
页数:17
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