From: Recent advances of engineered oncolytic viruses-based combination therapy for liver cancer
Different targeting strategies of gene therapy | Major genetic research targets | Research in gene therapy of liver cancer |
---|---|---|
Tumor-suppressor gene | Rb, p53, CDKN2A, DCC, Axin, VHL, WTl, MSH, MLH, HCCS1, APC | rAD-p53 has an adequate therapeutic effect on VX2 rabbit liver cancer [52] Ad5-PTEN inhibited the proliferation and migration of HepG2 cells and showed good anti-tumor activity on invasive HepG2 transplanted tumors in nude mice [58] Ad carrying TSLC1 gene inhibits the growth, migration, and invasion of HCC cells by downregulating the Wnt signaling pathway [56] |
Immune therapeutic gene | IL2, IL12, IL15, IL-24, IFNα, IFN-γ, IFN-β, TNF, CSF | rAd-IL-2 can stimulate the proliferation of T cells and production of memory T cells in mice with liver cancer and induce tumor-specific CTL reaction and IFN-γ secretion, thereby inhibiting the proliferation of HCC [64] AD-AFP-D55-IL-24 and AD-AFP-D55-TRAIL can induce cell apoptosis, which can significantly inhibit the tumor growth of Huh-7 cell xenograft mice [95] |
Suicide gene | CD/5-FC, HSV-TK/GCV, VZV-TK/ara-M, NTR/CB1954 | Ad-ETK expressing E1A and HSV-TK can resist HCC in vitro and in vivo, and HSV-TK/GCV enhances OAd therapy [80] AD-VEGFp-CDglyTK can effectively inhibit the growth of HCC cells and vascular endothelial cells in vitro and in vivo [82] |
Angiogenesis-related gene | Endostatin, angiostatin, arresten, integrin αγβ3, α-chemokine, bFGF, VEGF, PLGF, PDGF | Ad-DB7-shVEGF can reduce the expression of VEGF in HCC cells and induce an anti-angiogenesis effect in vitro and in vivo [90] ADK1-3 can inhibit the growth of HCC by intravenous injection in mice with HCC [91] |