Table 1 NRF2-active genetically engineered mouse models.
From: NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting
Genotype | Keap1 | Nfe2l2 | Phenotype | Reference |
|---|---|---|---|---|
Keap1flox/flox:: Trp53flox/flox:: R26tdTomato | CKO | WT | - Keap1/p53 deletion in airway basal stem cells produce lung SCC. - KEAP1 deletion increased tumor aggressiveness, metastasis, and resistance to radiotherapy | Jeong Cancer Discovery 2017 |
KrasLSL-G12D/+:: Tp53flox/flox with sgKeap1 | KO | WT | - Mouse model of LUAD - Increased tumor burden and aggressiveness | Romero Nature medicine 2017 |
Keap1fl/fl Ptenfl/fl | CKO | WT | - No phenotype with Keap1 loss alone - Combined loss of Keap1 and Pten produces lung adenocarcinoma | Best Cell Metabolism 2018 |
KrasLSL-G12D/+ p53fl/fl Keap1-Intratracheal Crispr KO | CKO | WT | - Intratracheally lentiviral delivery produced LUAD - Increased metastatic phenotype in KEAP1ko tumors - NRF2 activation promoted enhanced expression of Bach1 | Lignitto Cell 2019 |
KrasG12D Keap1fl/fl | CKO | WT | - KEAP1 deletion increased number of LUAD tumors of bronchiolar cell-of-origin - Reduced inflammatory response in KEAP1-KO tumors | Best Nature Communications 2019 |
KrasLSL-G12D/+ p53fl/fl Keap1fl/fl Slc33a1-KO | CKO | WT | - KEAP1-KO increased high-grade adenocarcinomas, tumor burden, tumor frequency - SLC33a1-KO decreased tumor burden and reduced number of high grade LUADs | Romero Nature Cancer 2020 |
LoxP-Stop-loxP KrasG12D Keap1FB/FB Keap1FA/FA | CKO | WT | - NRF2 activation in Kras-driven tumor cells promoted tumor growth and reduced survival - Activated host NRF2 in microenvironment suppressed tumor burden and prolonged survival | Hayashi Cancer Research 2020 |
KrasLSL-G12D Stk11fl/fl Keap1fl/fl | CKO | WT | - Keap1fl/flStk11fl/flKrasLSL-G12D mice demonstrate early, multifocal lung tumor development, mice develop progressive lung failure | Singh Clinical Cancer Research 2021 |
Trp53fl/fl p16fl/fl LSL-Nrf2E79Q/+ | WT | Transgene | - Mouse model of C-SCLC and P-SCLC. NRF2 silenced in C-SCLCs. Higher incidence of P-SCLCs in Nrf2E79Q/+ mice | Hamad Oncogene 2022 |
KrasG12D/+ Keap1R554Q Nrf2D29H | Conditional transgene | Conditional transgene | - Keap1R554Q/R554Q and Nrf2D29H/+ increased NSCLC tumor number in KrasG12D/+ model but disproportionately increased Grade 1 tumors and reduced Grade 3 tumors | DeBlasi Cancer Research 2023 |
KrasG12D/+ p53fl/fl KEAP1fl/fl | Conditional transgene | WT | - KEAP1+/fl tumors grew faster - Keap-KO associated with diminished immune responses | Zavitsanou Cell Reports 2023 |
NRF2L30F TRP53R172H Keap1-/- | KO | Transgene | - NRF2L30FTRP53R172H but not TRP53R172HKeap1-/- mice develop esophageal squamous cell carcinoma | Takahashi Cell Reports 2024 |
p16INK4A p53-/- NRF2E79Q | WT | Conditional Transgene | - p16INK4Ap53–/–NRF2E79Q but not p16INK4Ap53-/-NRF2+/+ mice develop oral squamous cell carcinoma | Hamad Cancer Research Communications 2024 |
