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Alterations of fibroblast growth factor receptors (FGFRs) are common in bladder and other cancers and result in disrupted signalling via several pathways. Therapeutics that target FGFRs have now entered the clinic, but, in common with many cancer therapies, resistance develops in most cases. To model this, we derived resistant sublines of two FGFR‐driven bladder cancer cell lines by long‐term culture with the FGFR inhibitor PD173074 and explored mechanisms using expression profiling and whole‐exome sequencing. We identified several resistance‐associated molecular profiles. These included HRAS mutation in one case and reversible mechanisms resembling a drug‐tolerant persister phenotype in others. Upregulated IGF1R expression in one resistant derivative was associated with sensitivity to linsitinib and a profile with upregulation of a YAP/TAZ signature to sensitivity to the YAP inhibitor CA3 in another. However, upregulation of other potential therapeutic targets was not indicative of sensitivity. Overall, the heterogeneity in resistance mechanisms and commonality of the persister state present a considerable challenge for personalised therapy. Nevertheless, the reversibility of resistance may indicate a benefit from treatment interruptions or retreatment following disease relapse in some patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Author(s): Alfred A. Antson [1, 2]; Julie E. Burns [2, 3]; Olga V. Moroz [1]; David J. Scott [1, 4]; Cyril M. Sanders [3]; Igor B. Bronstein [1]; G. Guy [...]

High blood levels of cholesterol (hypercholesterolemia) affect one in four adults in the United States and are considered a risk factor for the development of coronary artery disease. Dietary modification to reduce fat intake is the first step in lowering cholesterol levels, but other aspects of the diet are also under investigation for fat-reducing effects. Water-soluble fibers, such as those found in fruits, dried beans, legumes, barley, psyllium and oats, may lower fats and cholesterol in the blood. Oat cereals rich in beta-glucan are a potential dietary therapy for high cholesterol levels. To test how well oatmeal and oat bran lowered cholesterol, 148 adults with elevated levels of low-density lipoprotein cholesterol (LDL-C) completed a study during which they were given either one, two, or three ounces of oatmeal meal or oat bran, or one ounce of farina each day for 12 weeks. Beta-glucan, the water-soluble fiber in oat cereals, lowered cholesterol levels when taken in conjunction with a low-fat diet. Two ounces of oat bran lowered cholesterol better than one ounce, but three ounces did not produce a greater reduction. (This observation may be related to the small size of the study.) Three ounces of oatmeal were needed to reduce cholesterol as much as two ounces of oat bran. Theories about how soluble fiber reduces cholesterol are reviewed. It is also possible that the cholesterol-lowering effect is not related to beta-glucan, but to the effects of a compound with vitamin E activity or the amino acid content of oats, especially the arginine-lysine ratio. (Consumer Summary produced by Reliance Medical Information, Inc.)