| First Author | Germano G | Year | 2013 |
| Journal | Cancer Cell | Volume | 23 |
| Issue | 2 | Pages | 249-62 |
| PubMed ID | 23410977 | Mgi Jnum | J:194307 |
| Mgi Id | MGI:5473423 | Doi | 10.1016/j.ccr.2013.01.008 |
| Citation | Germano G, et al. (2013) Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23(2):249-62 |
| abstractText | There is widespread interest in macrophages as a therapeutic target in cancer. Here, we demonstrate that trabectedin, a recently approved chemotherapeutic agent, induces rapid apoptosis exclusively in mononuclear phagocytes. In four mouse tumor models, trabectedin caused selective depletion of monocytes/macrophages in blood, spleens, and tumors, with an associated reduction of angiogenesis. By using trabectedin-resistant tumor cells and myeloid cell transfer or depletion experiments, we demonstrate that cytotoxicity on mononuclear phagocytes is a key component of its antitumor activity. Monocyte depletion, including tumor-associated macrophages, was observed in treated tumor patients. Trabectedin activates caspase-8-dependent apoptosis; selectivity for monocytes versus neutrophils and lymphocytes is due to differential expression of signaling and decoy TRAIL receptors. This unexpected property may be exploited in different therapeutic strategies. |
