Table 1.
Potential cancer therapy by targeting necroptosis
| Cancer model | Small molecule | Major finding | Reference |
| Osteosarcoma | Shikonin | Shikonin increased tumor necrosis and repressed tumor growth of both primary and metastatic osteosarcomas in vivo | Fu et al., 2013 |
| Lung metastasis models of B16 and LLC1 | Nec-1 | Nec-1 reduced tumor cell-induced endothelial necroptosis and inhibited tumor cell extravasation and metastasis | Strilic et al., 2016 |
| 5-(2,3-Dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d] pyrimidin-4-amine (RIPK1 inhibitor) | This compound reduced the metastasis of B16 tumor cells in vivo | Li et al., 2018 | |
| AML | BV6 | BV6 activated TNF-dependent necroptosis in patient-derived AML blasts | Safferthal et al., 2017 |
| Nec-1 | Nec-1 in combination with IFN-γ significantly enhanced human primary AML cell differentiation and attenuated the clonogenic capacity | Xin et al., 2017 | |
| Breast cancer | NSA | NSA inhibited xenograft tumor growth of MDA-MB-231 in nude mice | Liu et al., 2016 |
| Colorectal cancer | Smac mimetic | Smac mimetic promoted the necroptosis of caspase-8-deficient colorectal cancer cells and inhibited the development of MC38 and ApcMin/+ mouse colorectal cancer | He et al., 2017 |
| GSK872 | GSK872 significantly reduced tumors in the spontaneous intestinal tumor model (ApcMin/+ mice) | Jayakumar and Bothwell, 2019 | |
| EL4, TC-1 | MTX | Cancer cell necroptosis induced by MTX exhibited the features of immunogenic cell death (ICD) and activated anticancer immune responses | Yang et al., 2016 |
| PDA | GSK'547 (RIPK1 inhibitor) | Inhibition of RIPK1 by GSK'547 induced immunogenic programming of TAMs, leading to activation of adaptive immune responses and tumor suppression. GSK'547 synergizes with PD-1 and ICOS-based Immunotherapy | Wang et al., 2018 |
LLC1: Lewis lung carcinoma line 1; Nec-1: necrostatin-1; AML: acute myeloid leukemia; TNF: tumor necrosis factor; IFN: interferon; NSA: necrosulfonamide; MTX: mitoxantrone; PDA: pancreatic ductal adenocarcinoma; RIPK: receptor-interacting protein (RIP) kinase; TAMs: tumor-associated macrophages; PD-1: checkpoint receptor; ICOS: co-stimulatory ligand