In vivo studies showed that C12 safely and effectively inhibited tumor growth in DU-145 and 22Rv1 xenograft models. In summary, C12 has been identified as a promising ADAR1 inhibitor for prostate cancer treatment.

Conclusions To our knowledge, AVA-ADR-001 is the first disclosure of a selective small molecule inhibitor of ADAR1 p150. AVA-ADR-001 is a potent and selective first-in-class ADAR1 inhibitor which has shown significant IFN induction in vitro and in vivo in the tumor microenvironment resulting in substantial tumor growth inhibition as monotherapy and synergistically in combination with Anti-PD1.

To our knowledge no selective small molecule inhibitors of ADAR1 have been reported so far and AVA-ADR-001 is the first disclosure of such an inhibitor. AVA-ADR-001 is a potent and selective first-in-class ADAR1 inhibitor which has shown significant IFN induction in various cancer cell lines and in vivo in the tumor microenvironment resulting in substantial tumor growth inhibition as monotherapy and synergistically in combination with Anti-PD1. Considering the immune-suppressive and pro-metastatic role of ADAR1, AVA-ADR-001 serves as a promising starting point for novel ADAR1 inhibitors as therapeutic modalities in cancer immunotherapy.

Treatments with mouse-specific ADAR1-, MSI2-siRNA-, or SLC38A4-expressing plasmids suppressed tumorigenesis and tumor growth in a mouse model of spontaneous liver cancer. Our findings suggest that the aberrant regulation of ADAR1 augments oncogenic MSI2 effects by excessively editing canonical miR-3144-3p and that the resultant ED_miR-3144-3p(3_A < G) simultaneously suppresses tumor suppressor SLC38A4 expression, contributing to hepatocellular carcinogenesis.

In summary, we showed that the survival benefit from DNMTi plus ADAR1 inhibition is dependent on type I IFN signaling. Thus, epigenetically inducing transposable element transcription combined with inhibition of RNA editing is a novel therapeutic strategy to reverse immune evasion in OC, a disease that does not respond to current immunotherapies.

In summary, these results suggest that LINC00624 is a cancer immunosuppressive lncRNA and targeting LINC00624 through ASOs in tumors expressing high levels of LINC00624 has great therapeutic potential in future clinical applications.

Besides, AAV9-CPEB3 induced hydropic degeneration in mouse liver, but did not cause kidney damage. These findings concluded that CPEB3 suppresses GC progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies.

We then examined the cytotoxic effects of anti-MM agents such as carfilzomib, pomalidomide, and HDAC inhibitors in RPMI 8226 cells with ADAR1 knockdown...Interestingly, IFN-a/b alone did not induce MM cell death but was able to enhance it by ADAR1 knockdown; however, MS-275 did not induce further cytotoxic effect of type I IFN in MM cells, indicating utilization of the same targets of ISGs with between HDAC1 inhibition and type I IFNstimulation in targeting ADAR1-dsRNA metabolic axis in MM cells. dsRNA overloading with ADAR1 inhibition may become a unique strategy targeting MM cells with Amp1q. Further study is warranted on the roles of ADAR1 for dsRNAediting and development of novel immunotherapies targeting dsRNA accumulation in high-risk MM.

Collectively, these results demonstrate that ADAR1 represses endogenous Z-RNAs and identifies ZBP1-mediated necroptosis as a new determinant of tumour immunogenicity masked by ADAR1. Therapeutic activation of ZBP1-induced necroptosis provides a readily translatable avenue for rekindling the immune responsiveness of ICB-resistant human cancers.

This survival benefit is a result of type I interferon signaling and CD8+ T cells. Thus, epigenetically inducing transposable element transcription, followed by inhibition of RNA editing, is a novel therapeutic strategy to reverse immune evasion in OC.