The IL6/Jak/STAT3 Signaling Axis Is a Therapeutic Vulnerability in SMARCB1-Deficient Bladder Cancer

SMARCB1 loss has long been observed in many solid tumors. However, there is a need to elucidate targetable pathways driving growth and metastasis in SMARCB1-deficient tumors. Here, we demonstrate that SMARCB1 deficiency, defined as genomic SMARCB1 copy number loss associated with reduced mRNA, drives disease progression in patients with bladder cancer by engaging STAT3. SMARCB1 loss increases the chromatin accessibility of the STAT3 locus in vitro. Orthotopically implanted SMARCB1 knockout (KO) cell lines exhibit increased tumor growth and metastasis. SMARCB1-deficient tumors show an increased IL6/JAK/STAT3 signaling axis in in vivo models and patients. Furthermore, a pSTAT3 selective inhibitor, TTI-101, reduces tumor growth in SMARCB1 KO orthotopic cell line-derived xenografts and a SMARCB1-deficient patient derived xenograft model. We have identified a gene signature generated from SMARCB1 KO tumors that predicts SMARCB1 deficiency in patients. Overall, these findings support the clinical evaluation of STAT3 inhibitors for the treatment of SMARCB1-deficient bladder cancer

Planar perovskite solar cells with long-term stability using ionic liquid additives

Solar cells based on metal halide perovskites are one of the most promising photovoltaic technologies1,2,3,4. Over the past few years, the long-term operational stability of such devices has been greatly improved by tuning the composition of the perovskites5,6,7,8,9, optimizing the interfaces within the device structures10,11,12,13, and using new encapsulation techniques14,15. However, further improvements are required in order to deliver a longer-lasting technology. Ion migration in the perovskite active layer—especially under illumination and heat—is arguably the most difficult aspect to mitigate16,17,18. Here we incorporate ionic liquids into the perovskite film and thence into positive–intrinsic–negative photovoltaic devices, increasing the device efficiency and markedly improving the long-term device stability. Specifically, we observe a degradation in performance of only around five per cent for the most stable encapsulated device under continuous simulated full-spectrum sunlight for more than 1,800 hours at 70 to 75 degrees Celsius, and estimate that the time required for the device to drop to eighty per cent of its peak performance is about 5,200 hours. Our demonstration of long-term operational, stable solar cells under intense conditions is a key step towards a reliable perovskite photovoltaic technology