| First Author | He GW | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 6 | Pages | 1655-1662 |
| PubMed ID | 28476895 | Mgi Jnum | J:243778 |
| Mgi Id | MGI:5912557 | Doi | 10.1084/jem.20160442 |
| Citation | He GW, et al. (2017) Regression of apoptosis-resistant colorectal tumors by induction of necroptosis in mice. J Exp Med 214(6):1655-1662 |
| abstractText | Cancer cells often acquire capabilities to evade cell death induced by current chemotherapeutic treatment approaches. Caspase-8, a central initiator of death receptor-mediated apoptosis, for example, is frequently inactivated in human cancers via multiple mechanisms such as mutation. Here, we show an approach to overcome cell death resistance in caspase-8-deficient colorectal cancer (CRC) by induction of necroptosis. In both a hereditary and a xenograft mouse model of caspase-8-deficient CRC, second mitochondria-derived activator of caspase (SMAC) mimetic treatment induced massive cell death and led to regression of tumors. We further demonstrate that receptor-interacting protein kinase 3 (RIP3), which is highly expressed in mouse models of CRC and in a subset of human CRC cell lines, is the deciding factor of cancer cell susceptibility to SMAC mimetic-induced necroptosis. Thus, our data implicate that it may be worthwhile to selectively evaluate the efficacy of SMAC mimetic treatment in CRC patients with caspase-8 deficiency in clinical trials for the development of more effective personalized therapy. |
