Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-dependent cell lines display increased expression of interferon-stimulated genes. Activation of type I interferon signaling in the context of ADAR1 deficiency can induce cell lethality in non-ADAR1-dependent cell lines. ADAR deletion causes activation of the double-stranded RNA sensor, protein kinase R (PKR). Disruption of PKR signaling, through inactivation of PKR or overexpression of either a wildtype or catalytically inactive mutant version of the p150 isoform of ADAR1, partially rescues cell lethality after ADAR1 loss, suggesting that both catalytic and non-enzymatic functions of ADAR1 may contribute to preventing PKR-mediated cell lethality. Together, these data nominate ADAR1 as a potential therapeutic target in a subset of cancers.

The PPARG gene encoding the nuclear receptor PPAR-gamma is activated in bladder cancer, either directly by gene amplification or mutation, or indirectly by mutation of the RXRA gene which encodes the heterodimeric partner of PPAR-gamma. Here we show that activating alterations of PPARG or RXRA lead to a specific gene expression signature in bladder cancers. Reducing PPARG activity, whether by pharmacologic inhibition or genetic ablation, inhibited proliferation of PPARG-activated bladder cancer cells. Our results offer a preclinical proof of concept for PPARG as a candidate therapeutic target in bladder cancer.

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We report the reduction of surface reflection losses in zinc germanium phosphide (ZnGeP2, or ZGP) crystals by fabricating an antireflection (AR) structure in the substrate itself using subwavelength motheye surface patterns. The motheye AR patterning works by creating a region of gradually varying effective refractive index between air and the ternary nonlinear crystal. Motheye structures were created using interference lithography and reactive-ion etching in a SiCl4 plasma. The ZGP crystal with motheye patterning on the output surface reached a transmittance of ∼67% at a cutoff wavelength of 3.8 μm (close to the theoretical maximum of 73%), with negligible surface contamination from the motheye etching process. The motheye patterning technique could be applied to other nonlinear crystals where surface reflection losses are a concern.