Thompsonjoyce9474

This review aims at updating on the most recently discovered mechanisms of tumorigenesis and the pivotal role of GxE interactions. 2020 Translational Lung Cancer Research. All rights reserved.Research has established a strong association between asbestos exposure and malignant mesothelioma, a deadly form of cancer. Since the early 1980's many countries have restricted or banned the production of asbestos, leading to a decline of occupational asbestos exposure in many industrialized countries. However, some countries continue to use asbestos, and worldwide rates of mesothelioma are still increasing. Because of the long latency between exposure and mesothelioma occurrence and the persistence of environmental exposure, incidence rates (IR) may decrease very slowly for several years ahead. In this review, we examine estimates of asbestos consumption before widespread asbestos regulations and the trends in incidence and mortality rates, as well as changes over time for the United States and Europe. In some countries with earlier asbestos restrictions, mesothelioma incidence has been in a modest decline over time. However, asbestos exposure is still a burden worldwide and legislative action is needed to obtain a full ban. The pattern of mesothelioma is shifting from a mostly male disease to a disease that affects females as well in substantial numbers. Studies on unknown sources of asbestos exposure, of other sources of natural exposure to asbestos and asbestos-like fibers, as well as of individual genetic susceptibility to asbestos fibers are needed. 2020 Translational Lung Cancer Research. All rights reserved.Immunohistochemistry plays an indispensable role in accurate diagnosis of malignant mesothelioma, particularly in morphologically challenging cases and in biopsy and cytology specimens, where tumor architecture is difficult or impossible to evaluate. Application of a targeted panel of mesothelial- and epithelial-specific markers permits correct identification of tumor lineage in the vast majority of cases. An immunopanel including two mesothelial markers (calretinin, CK5/6, WT-1, or D2-40) and two epithelial markers (MOC-31 and claudin-4) offers good sensitivity and specificity, with adjustments as appropriate for the differential diagnosis. Once mesothelial lineage is established, malignancy-specific studies can help verify a diagnosis of malignant mesothelioma. BAP1 loss, CDKN2A homozygous deletion, and MTAP loss are highly specific markers of malignancy in a mesothelial lesion, and they attain acceptable diagnostic sensitivity when applied as a diagnostic panel. Novel markers of malignancy, such as 5-hmC loss and increased EZH2 expression, are promising, but have not yet achieved widespread clinical adoption. Some diagnostic markers also have prognostic significance, and PD-L1 immunohistochemistry may predict tumor response to immunotherapy. buy JSH-23 Application and interpretation of these immnuomarkers should always be guided by clinical history, radiographic findings, and above all histomorphology. 2020 Translational Lung Cancer Research. All rights reserved.The efficacy and safety of osimertinib have been demonstrated in several clinical trials; however, acquired resistance is an inevitable problem associated with most targeted drugs. Based on previous findings, the mechanism of osimertinib resistance is equivocal, and there is still no consensus on the most optimal treatment strategy after developing resistance, especially for patients detected with no actionable driver mutation. Here, we report the efficacy of erlotinib rechallenge in a patient with advanced lung adenocarcinoma following osimertinib resistance mediated by driver gene loss. Following osimertinib resistance, targeted sequencing of both blood and tissue samples revealed the disappearance of both EGFR exon 19 deletion and T790M. Erlotinib was then re-administered, achieving partial response for 26 months at least. Our case provides clinical evidence supporting the efficacy of erlotinib rechallenges in overcoming osimertinib resistance mediated by driver gene loss, which may translate into novel treatment strategies for lung cancer patients following development of resistance to osimertinib. 2020 Translational Lung Cancer Research. All rights reserved.Epithelial growth factor receptor (EGFR) T790M mutation and small cell lung cancer (SCLC) transformation are well-known resistance mechanisms acquired during treatment with EGFR tyrosine kinase inhibitors (TKIs). Various mechanisms sometimes coexist in patients. Here, we report a 57-year-old female diagnosed with stage IV lung adenocarcinoma, who harbored an EGFR exon 19 deletion mutation. This patient initially received gefitinib and progressed after 14 months. A repeat biopsy was performed, and the original EGFR exon 19 deletion and acquired exon 20 T790M mutation were identified. Then, pemetrexed plus carboplatin was administered as second-line and osimertinib as third-line treatment. Rapid progression and mixed response were observed after 2 months on osimertinib, with stable disease of the primary lung lesion but rapid growth of a right lower chest mass. The progressive chest lesion underwent biopsy, and the SCLC transformation was revealed. Furthermore, the patient was treated with etoposide and cisplatin, and she achieved disease control for 4 months. A fourth biopsy both for the primary lung lesion and the chest mass were finally conducted. Interestingly, the histopathology of the two different lesions showed adenocarcinoma and SCLC, respectively. The patient then rapidly suffered brain metastasis, and no EGFR mutations were detected in her cerebrospinal fluid (CSF). Overall survival (OS) of the patient was 29 months. This patient experienced concomitant resistance mechanisms of T790M mutation and SCLC transformation, which might have resulted from intra-tumor heterogeneity and drug-induced selection. Ultimately, this case reminds us that repeat biopsies are essential for patients receiving EGFR-TKIs in order to make appropriate treatment decisions according to the diverse mechanisms of acquired resistance. 2020 Translational Lung Cancer Research. All rights reserved.