Programmed cell death-1/Programmed cell death ligand-1(PD-1/PD-L1) inhibitors, heralding a new era of immunotherapy in the management of advanced Non-Small Cell Lung Cancer (NSCLC)

Ogunleye, Foluso; Blankenship, Leann; Millisor, Vanessa E.; Anderson, Joseph M; Jaiyesimi, Ishmael

doi:10.1016/j.ctarc.2017.05.002

Cited by 9 publications

(13 citation statements)

References 66 publications

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“…Chemotherapy is used as the standard treatment for most patients with advanced disease, but its effect is limited because of unsatisfactory efficacy and side effects [ 5 ]. In the last decade, new therapies that have been developed for advanced NSCLC treatment, including targeted therapy and immunotherapy, have shown better clinical effects in terms of the objective response rate and prolonging survival in comparison with conventional chemotherapy [ 6 , 7 ]. Several oncogenic drivers of NSCLC, such as the epidermal growth factor receptor (EGFR) and BRAF mutations, as well as anaplastic lymphoma kinase (ALK) and ROS-1 rearrangements, have been uncovered and studied.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, targeted therapies, including those based on the use of EGFR-tyrosine kinase inhibitors (TKIs), BRAF inhibitors, and ALK inhibitors, have demonstrated promising efficacy, with a 60–80% response rate and 9–30 months of progression-free survival in treating advanced NSCLC with relevant driver mutations [ 6 , 8 , 9 ]. Immunotherapy using anti-PD-1/PD-L1 immune checkpoint inhibitors has been developed as a new therapy for metastatic NSCLC that has demonstrated efficacy in numerous clinical trials in which a 15–45% objective response rate was observed in addition to prolonged overall survival [ 7 , 10 , 11 , 12 ]. However, some NSCLC patients still do not have targetable driver mutations and do not benefit from immunotherapy [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Hsu

Yang

Jablons

et al. 2020

Cancers

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The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Hsu

Yang

Jablons

et al. 2020

Cancers

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“…cancers including non-small-cell lung cancer, melanoma, renal cell carcinoma and Hodgkin lymphoma. [6][7][8][9][10] Recently, PD-1/PD-L1 inhibitors were also used to treat patients with advanced MPM, and several clinical trials are ongoing. 11,12 Tumour PD-L1 expression has been used as a predictive biomarker for PD-1/PD-L1 inhibitors.…”

mentioning

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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“…In normal human tissue cells, the binding of PD-L1 and PD-1 promotes T-cell tolerance by downregulating CD8+ T-cell survival and effector function [11]. PD-L1 expression has been reported to appear in human NSCLC, and NSCLC cells can escape the anti-tumor immune response of their host by engaging the immune checkpoint PD-L1/PD-1 axis [12][13][14]. In response, anti -PD-L1/PD-1 immune checkpoint inhibitors have been developed as new therapies for advanced NSCLC [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…PD-L1 expression has been reported to appear in human NSCLC, and NSCLC cells can escape the anti-tumor immune response of their host by engaging the immune checkpoint PD-L1/PD-1 axis [12][13][14]. In response, anti -PD-L1/PD-1 immune checkpoint inhibitors have been developed as new therapies for advanced NSCLC [13][14][15][16][17][18]. PD-L1 expression on NSCLC tumor surfaces has been used as a predictive biomarker for anti-PD-L1/PD-1 immunotherapy, and PD-L1-positive NSCLC is correlated with a higher response to anti-PD-L1/PD-1 immunotherapy [15,19].…”

Section: Introductionmentioning

confidence: 99%

The Co-Expression of Programmed Death-Ligand 1 (PD-L1) in Untreated EGFR-Mutated Metastatic Lung Adenocarcinoma

et al. 2020

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Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is the standard first-line therapy for metastatic lung adenocarcinoma harboring sensitive EGFR mutations. Tumor surface programmed death-ligand 1 (PD-L1) is expressed in some metastatic EGFR-mutated lung adenocarcinoma, but its impact on the efficacy of EGFR-TKIs is unclear. We retrospectively investigated 117 untreated metastatic lung EGFR mutated adenocarcinoma patients with a PD-L1 immunohistochemistry test. The PD-L1 expression level was classified by tumor proportion scores (TPS). Forty-five patients had negative expression (TPS < 1%), 45 had a weak expression (TPS 1–49%), and 27 had a strong expression (≥50%). All patients recruited in this study received EGFR-TKIs as a first-line therapy. No significant differences were observed for objective response rates (68.9% versus 62.2% versus 73.1%, p = 0.807) and median time to treatment failure (TTF) (12.17 versus 13.17 versus 11.0 months, p = 0.443) of first-line EGFR-TKIS among the three groups of patients (negative versus weak versus strong). The median overall survival was 21.27 versus 20.63 versus 19.43 months among the three groups of patients (p = 0.77). Our results demonstrated that PD-L1 did not affect the efficacy of first-line EGFR-TKIs in metastatic EGFR mutated lung adenocarcinoma. Thus, EGFR-TKIs are suggested as the preferred clinical therapy for these patients, despite their PD-L1 levels.

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Programmed cell death-1/Programmed cell death ligand-1(PD-1/PD-L1) inhibitors, heralding a new era of immunotherapy in the management of advanced Non-Small Cell Lung Cancer (NSCLC)

Cited by 9 publications

References 66 publications

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

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

The Co-Expression of Programmed Death-Ligand 1 (PD-L1) in Untreated EGFR-Mutated Metastatic Lung Adenocarcinoma

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