Novel systemic therapy against malignant pleural mesothelioma

Mancuso, Michael R.; Neal, Joel W.

doi:10.21037/tlcr.2017.06.01

Cited by 23 publications

(26 citation statements)

References 174 publications

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“…Small sample size among the non-pleural mesothelioma group also precluded more in-depth analyses to identify factors associated with treatment and survival among these patients. Finally, the patients included in this study were diagnosed in 2011 prior to the publication of promising clinical trials; 18 thus, the current findings may not accurately represent current treatment patterns.…”

Section: Discussionmentioning

confidence: 98%

Patterns of care and survival among patients with malignant mesothelioma in the United States

2017

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Background Mesothelioma is a rare malignancy that is associated with poor survival. This study aimed to describe the patterns of care and subsequent survival among malignant mesothelioma patients in the United States, while adjusting for patient demographics and comorbidities. Methods A random sample of patients diagnosed with histologically confirmed mesothelioma in 2011, as reported to the National Cancer Institute’s Surveillance Epidemiology and End Results program, were included. Logistic regression and Cox proportional hazard regression were utilized to identify factors associated with receipt of therapy and all-cause mortality, respectively, among patients with pleural mesothelioma. Results This study included 389 patients with pleural mesothelioma and 53 patients with non-pleural mesothelioma. Almost a third (29.3%) of the pleural patients and 21.5% of the non-pleural patients received no therapy. Additionally, approximately 60% of both patient groups received systemic therapy. Among pleural mesothelioma patients, receipt of therapy was less likely among older patients. Median survival was 9 months among the pleural patients and 18 months among the non-pleural patients. Receipt of either surgery or systemic therapy and particularly the combination of these two modalities was associated with better all-cause survival. Additionally, among pleural mesothelioma patients, younger age and lower socioeconomic status were found to be associated with better all-cause survival. Comorbidity score was not found to be associated with receipt of treatment nor was it independently associated with survival among pleural mesothelioma patients. Conclusion These findings indicate the need for efforts to ensure equitable application of currently available therapies to all patients.

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Section: Discussionmentioning

confidence: 98%

Patterns of care and survival among patients with malignant mesothelioma in the United States

2017

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“…However, these patient samples were initially studied 10‐20 years ago, and there was not enough tissue left to evaluate the further molecular status between YAP and PD‐L1. Although PD‐1/PD‐L1 inhibitors can be a new treatment option for unresectable MPM with high PD‐L1 expression, the efficacy of PD‐1/PD‐L1 inhibitors is under investigation in clinical trials currently 11, 25, 26. After these clinical trials completed and even anti‐PD‐1/PD‐L1 inhibitors are approved in treating patients with advanced MPM, more patient samples should be gathered to investigate the molecular relevance between YAP and PD‐L1 in the future.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of yes‐associated protein down‐regulates PD‐L1 (CD274) expression in human malignant pleural mesothelioma

Hsu

Miao

Wang

et al. 2018

J Cellular Molecular Medi

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Although tumour PD‐L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD‐L1 axis in various cancers, the regulation of PD‐L1 (CD274) expression is unclear. Yes‐associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down‐regulates PD‐L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD‐L1 protein expression compared to H290, MS‐1 and H28 cells. In H2052 and 211H cells, PD‐L1 mRNA expression was significantly increased compared to other MPM cell lines; YAP knockdown by small interfering RNA decreased PD‐L1 protein and mRNA expression. Forced overexpression of the YAP gene increased PD‐L1 protein expression in H2452 cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD‐L1 enhancer region encompassing 2 putative YAP‐TEAD‐binding sites in H2052 cells. We found that, in human MPM tissue microarray samples, YAP and PD‐L1 concurrently expressed in immunohistochemistry stain (n = 70, P < .05, chi‐square). We conclude that PD‐L1 is correlated with YAP expression, and inhibition of YAP down‐regulates PD‐L1 expression in human MPM. Further study of how YAP regulates PD‐L1 in MPM is warranted.

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“…The combination of cisplatin plus gemcitabine was also evaluated in some phase II trials suggesting that it may be an alternative in patients not candidates to pemetrexed, despite heterogeneity between studies with response rates and survival ranging from 12-48% and 9.5-12 months, respectively (3,(27)(28)(29)(30)(31). Furthermore, the use of carboplatin with gemcitabine has been investigated showing good tolerance and a response rate of 26% (32).…”

Section: First-line Combination Ctmentioning

confidence: 99%

“…Males are 3.8 times more affected than females and have a worse survival rate (2,3). Moreover, two prognostic scoring systems published from EORTC and CALGB include pleural primary site, high serum level of LDH, poor ECOG performance status, high serum levels of platelets, non-epithelial histology and advanced age as independent predictors of poor outcome (4,5).…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy treatment in malignant pleural mesothelioma: a difficult history

et al. 2018

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Malignant pleural mesothelioma (MPM) is a rare neoplasm that typically arises from mesothelial surfaces of the pleural cavity. Despite treatment improvements, it carries a dismal prognosis. The majority of patients either have unresectable disease or are not candidates for surgery due to medical comorbidities or old age. For such patients, chemotherapy (CT) represents the gold-standard treatment. To date, combination CT with cisplatin plus pemetrexed represents the most widely used regimen in first-line setting for patients with unresectable MPM. Other first-line options are currently available, including the use of raltitrexed instead of pemetrexed combined with platinum. In this review, we discuss the role of CT in MPM mainly focusing on the results of the trials conducted in first-line setting.

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Novel systemic therapy against malignant pleural mesothelioma

Cited by 23 publications

References 174 publications

Patterns of care and survival among patients with malignant mesothelioma in the United States

Patterns of care and survival among patients with malignant mesothelioma in the United States

Inhibition of yes‐associated protein down‐regulates PD‐L1 (CD274) expression in human malignant pleural mesothelioma

Chemotherapy treatment in malignant pleural mesothelioma: a difficult history

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