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Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies. [ABSTRACT FROM AUTHOR]

Pleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: A systematic review and meta-analysis were performed to determine the diagnostic performance of dynamic contrast-enhanced computed tomography (DCE-CT) for the differentiation between malignant and benign pulmonary nodules.Methods: Ovid MEDLINE and EMBASE were searched for studies published up to October 2018 on the diagnostic accuracy of DCE-CT for the characterisation of pulmonary nodules. For the index test, studies with a minimum of a pre- and post-contrast computed tomography scan were evaluated. Studies with a reference standard of biopsy for malignancy, and biopsy or 2-year follow-up for benign disease were included. Study bias was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). The sensitivities, specificities, and diagnostic odds ratios were determined along with 95% confidence intervals (CIs) using a bivariate random effects model.Results: Twenty-three studies were included, including 2397 study participants with 2514 nodules of which 55.3% were malignant (1389/2514). The pooled accuracy results were sensitivity 94.8% (95% CI 91.5; 96.9), specificity 75.5% (69.4; 80.6), and diagnostic odds ratio 56.6 (24.2-88.9). QUADAS 2 assessment showed intermediate/high risk of bias in a large proportion of the studies (52-78% across the domains). No difference was present in sensitivity or specificity between subgroups when studies were split based on CT technique, sample size, nodule size, or publication date.Conclusion: DCE-CT has a high diagnostic accuracy for the diagnosis of pulmonary nodules although study quality was indeterminate in a large number of cases.Key Points: • The pooled accuracy results were sensitivity 95.1% and specificity 73.8% although individual studies showed wide ranges of values. • This is comparable to the results of previous meta-analyses of PET/CT (positron emission tomography/computed tomography) diagnostic accuracy for the diagnosis of solitary pulmonary nodules. • Robust direct comparative accuracy and cost-effectiveness studies are warranted to determine the optimal use of DCE-CT and PET/CT in the diagnosis of SPNs. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-98414-w, published online 27 September 2021 The original version of this Article contained an error. In the Results section, under subheading 'High level of VISTA is frequent in epithelioid mesothelioma and its expression level correlates with Hedgehog and immune pathway components', "Ki67 correlated with copy number burden ( I P i = 0.03, r = 0.42) and with MTAP score ( I P i = 0.04, r = 0.39), consistent with disordered cellular division accompanying I CDKN2A i deletion." now reads: "Ki67 correlated with copy number burden ( I P i = 0.03, r = 0.42) and with MTAP score ( I P i = 0.04, r = - 0.39), consistent with disordered cellular division accompanying I CDKN2A i deletion.". [Extracted from the article]

Resistance to chemotherapy is a principal problem in the treatment of small cell lung cancer (SCLC). We show here that SCLC is surrounded by an extensive stroma of extracellular matrix (ECM) at both primary and metastatic sites. Adhesion of SCLC cells to ECM enhances tumorigenicity and confers resistance to chemotherapeutic agents as a result of β1 integrin-stimulated tyrosine kinase activation suppressing chemotherapy-induced apoptosis. SCLC may create a specialized microenvironment, and the survival of cells bound to ECM could explain the partial responses and local recurrence of SCLC often seen clinically after chemotherapy. Strategies based on blocking β1 integrin-mediated survival signals may represent a new therapeutic approach to improve the response to chemotherapy in SCLC. [ABSTRACT FROM AUTHOR]