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https://www.readbyqxmd.com/read/28932563/a-systematic-and-genome-wide-correlation-meta-analysis-of-pd-l1-expression-and-targetable-nsclc-driver-genes
#1
Jin Li, Yaoqi Chen, Xiaoshun Shi, Xiaobing Le, Fenglan Feng, Jingyi Chen, Chengzhi Zhou, Yusong Chen, Shuai Wen, Haikang Zeng, Allen M Chen, Yu Zhang
BACKGROUND: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. METHODS: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28915714/the-efficacy-of-anti-pd-1-pd-l1-therapy-and-its-comparison-with-egfr-tkis-for-advanced-non-small-cell-lung-cancer
#2
REVIEW
Zhixin Sheng, Xu Zhu, Yanhua Sun, Yanxia Zhang
PURPOSE: To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). METHODS: The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. RESULTS: Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912396/-immune-checkpoint-inhibitors-for-lung-cancer-with-egfr-mutation
#3
Hidetoshi Hayashi, Tetsuya Mitsudomi
Recent clinical evidence that anti-PD-1/PD-L1 antibody therapy is superior to cytotoxic chemotherapy for patients with non-small cell lung cancer(NSCLC)that expresses PD-L1 has lead to a paradigm shift in treatment strategies for those patients. However, efficacy of anti-PD-1/PD-L1 antibodies for patients with NSCLC harboring EGFR mutation is generally poor. This lack ofresponse is at least partially attributed to suppression oftumor infiltrating lymphocytes caused by EGFR pathway activation or to low non-synonymous mutation load in NSCLC with EGFR mutation...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28901258/from-biology-to-therapy-improvements-of-therapeutic-options-in-lung-cancer
#4
Luigi Formisano, Valerie M Jansen, Roberta Marciano, Roberto Bianco
Lung cancer is the leading cause of cancer-related mortality around the world, despite effective chemotherapeutic agents, the prognosis has remained poor for a long time. The discovery of molecular changes that drive lung cancer has led to a dramatic shift in the therapeutic landscape of this disease. In "in vitro" and "in vivo" models of NSCLC (non-small cell lung cancer), angiogenesis blockade has demonstrated an excellent anti-tumor activity, thus, a number of anti-angiogenic drugs have been approved by regulatory authorities for use in clinical practice...
September 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28881856/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#5
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880262/acceleration-of-pancreatic-tumorigenesis-under-immunosuppressive-microenvironment-induced-by-reg3g-overexpression
#6
Xiulan Liu, Zhongshi Zhou, Qi Cheng, Hongjie Wang, Hui Cao, Qianqian Xu, Yali Tuo, Li Jiang, You Zou, Hongyu Ren, Ming Xiang
Reg3g is a potential risk for pancreatic ductal adenocarcinoma (PDAC). We previously demonstrated that Reg3g promoted pancreatic carcinogenesis via a STAT3 signaling pathway in a murine model of chronic pancreatitis. Whether the immune response is involved in tumorigenesis induced by Reg3g remains unknown. In this study, Reg3g-regulated tumor immunity was evaluated in tumor-implanted murine models, immune cells, and tumor microenvironment. In mice that had been orthotopically or ectopically implanted with Panc02 cells, Reg3g overexpression increased EGFR and Ki67, diminished MHC-I and caspase-3 expression, and accelerated growth of tumors...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28880013/osimertinib-azd9291-decreases-programmed-death-ligand-1-in-egfr-mutated-non-small-cell-lung-cancer-cells
#7
Xiao-Ming Jiang, Yu-Lian Xu, Mu-Yang Huang, Le-Le Zhang, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1). Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro. Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28860576/pd-l1-expression-in-lung-cancer-and-its-correlation-with-driver-mutations-a-meta-analysis
#8
Minghui Zhang, Guoliang Li, Yanbo Wang, Yan Wang, Shu Zhao, Pu Haihong, Hongli Zhao, Yan Wang
Although many studies have addressed the prognostic value of programmed cell death-ligand 1 (PD-L1) expression in lung cancer, the results remain controversial. A systematic search of the PubMed, EMBASE, and Cochrane Library databases was performed to identify the correlation between PD-L1 expression and driver mutations and overall survival (OS). This meta-analysis enrolled a total of 11,444 patients for 47 studies, and the pooled results showed that increased PD-L1 expression was associated with poor prognosis (HR = 1...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28840016/lung-adenocarcinoma-from-molecular-basis-to-genome-guided-therapy-and-immunotherapy
#9
REVIEW
Roberto Chalela, Víctor Curull, César Enríquez, Lara Pijuan, Beatriz Bellosillo, Joaquim Gea
Although adenocarcinoma (ADC) is the most frequent lung cancer, its diagnosis is often late, when the local invasion is important and/or the metastases have already appeared. Therefore, the mortality at 5 years is still very high, ranging from 51% to 99%, depending on the stage. The implementation of different molecular techniques has allowed genomic studies even in relatively small histological samples such as obtained with non-invasive or minimally invasive techniques, facilitating a better phenotyping of lung ADC...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28838391/programmed-death-ligand-1-expression-and-t790m-status-in-egfr-mutant-non-small-cell-lung-cancer
#10
Akito Hata, Nobuyuki Katakami, Shigeki Nanjo, Chiyuki Okuda, Reiko Kaji, Katsuhiro Masago, Shiro Fujita, Hiroshi Yoshida, Kota Zama, Yukihiro Imai, Yukio Hirata
BACKGROUND: Differential biology and prognosis between T790M+ and T790M- populations imply immunological differences also. METHODS: We retrospectively analyzed programmed death-ligand 1 (PD-L1) expression and T790M status in rebiopsied samples of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). PD-L1 immunohistochemistry was performed using the SP142 antibody for tumour cell (TC) and tumour-infiltrating immune cell (IC) and the 28-8 antibody for TC...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28835513/fda-approval-summary-pembrolizumab-for-treatment-of-metastatic-non-small-cell-lung-cancer-first-line-therapy-and-beyond
#11
Lee Pai-Scherf, Gideon M Blumenthal, Hongshan Li, Sriram Subramaniam, Pallavi S Mishra-Kalyani, Kun He, Hong Zhao, Jingyu Yu, Mark Paciga, Kirsten B Goldberg, Amy E McKee, Patricia Keegan, Richard Pazdur
On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy...
August 23, 2017: Oncologist
https://www.readbyqxmd.com/read/28828496/impact-of-postoperative-radiotherapy-and-her2-new-overexpression-in-salivary-duct-carcinoma-a%C3%A2-monocentric-clinicopathologic-analysis
#12
Marlen Haderlein, Claudia Scherl, Sabine Semrau, Sebastian Lettmaier, Markus Hecht, Ramona Erber, Heinrich Iro, Rainer Fietkau, Abbas Agaimy
AIM: Retrospective Investigation of the prognostic relevance of clinicopathologic parameters in patients with salivary duct carcinoma (SDC). METHODS: An experienced pathologist reviewed 67 patients with de novo SDC or SDC ex pleomorphic adenoma. Paraffin-embedded tumor samples were examined by immunohistochemistry for expression of HER2/neu, androgen (AR), progesterone (PR), estrogen (ER), epidermal growth factor (EGFR) and programmed death ligand 1 (PD-L1-R) receptor...
August 21, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28819374/variant-cd44-expression-is-enriching-for-a-cell-population-with-cancer-stem-cell-like-characteristics-in-human-lung-adenocarcinoma
#13
Makoto Nishino, Mari Ozaki, Ahmed E Hegab, Junko Hamamoto, Shizuko Kagawa, Daisuke Arai, Hiroyuki Yasuda, Katsuhiko Naoki, Kenzo Soejima, Hideyuki Saya, Tomoko Betsuyaku
Background: Preliminary studies have identified cancer stem cells (CSCs) in various cancers and there are several ongoing clinical studies targeting these cells. CD44 (standard or variant isoforms) and/or aldehyde dehydrogenase (ALDH) expression is the most commonly used markers for the identification of CSCs. The goal of the current study was to examine the ability of CD44v, either alone or in combination with ALDH, to identify CSCs within human lung cancer cells lines. Methods: We examined several lung adenocarcinoma cell lines for the ability of CD44v and/or ALDH expression to enrich for cells with CSC characteristics such as in vitro differential proliferation rate, chemotherapeutic-resistance, tumorsphere formation, and in vivo tumorigenicity...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28808573/osimertinib-induced-interstitial-lung-disease-in-a-patient-with-non-small-cell-lung-cancer-pretreated-with-nivolumab-a-case-report
#14
Osamu Takakuwa, Tetsuya Oguri, Takehiro Uemura, Kazuki Sone, Satoshi Fukuda, Minami Okayama, Yoshihiro Kanemitsu, Hirotsugu Ohkubo, Masaya Takemura, Yutaka Ito, Ken Maeno, Akio Niimi
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#15
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28761805/egfr-or-pd-l1-decision-for-first-line-therapy-in-a-case-series-of-egfr-positive-and-pd-l1-50
#16
Paul Zarogoulidis, Panos Chinelis, Christofors Efthymiou, Anastasia Athanasiadou, Vasilis Mpikos, George Papatsibas, Vasilis Papadopoulos, Elena Maragouli, Haidong Huang, Georgia Trakada, Anastasios Kallianos, Lemonia Veletza, Wolfgang Hohenforst-Schmidt
Targeted therapies are on the market for the past five years and recently pembrolizumab was approved as first line treatment for patients with PD-L1 >50%. We present three cases of patients which had epidermal growth factor receptor positive expression and programmed death-ligand 1 (PD-L1), PD-L1 >50% overexpression.
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28756492/large-scale-comprehensive-immunohistochemical-biomarker-analyses-in-esophageal-squamous-cell-carcinoma
#17
Ken Hatogai, Satoshi Fujii, Takashi Kojima, Hiroyuki Daiko, Shogo Nomura, Toshihiko Doi, Shigehisa Kitano, Atsushi Ohtsu, Yuichi Takiguchi, Takayuki Yoshino, Atsushi Ochiai
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a heterogeneous disease in the sense that the biological behavior is regulated by the activation of various signaling pathways. The aim of this study was to investigate the relationships between the expressions of various targetable proteins and the clinicopathological characteristics of ESCC patients. METHODS: A total of 286 patients with ESCC who had undergone curative surgical resection without neoadjuvant therapy were enrolled in this study...
July 29, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28756224/treatment-with-a-programmed-cell-death-1-specific-antibody-has-little-effect-on-afatinib-and-naphthalene-induced-acute-pneumonitis-in-mice
#18
Naoki Hamada, Toyoshi Yanagihara, Kunihiro Suzuki, Saiko Ogata-Suetsugu, Eiji Harada, Hironori Mikumo, Masako Arimura-Omori, Yoichi Nakanishi
Although several antibodies developed to target programmed cell death-1 (PD-1) and its ligand (PD-L1) have demonstrated great promise for the treatment of non-small cell lung cancer (NSCLC), and other malignancies, these therapeutic antibodies can cause pneumonitis. Furthermore, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced pneumonitis was reported after treatment with anti PD-1 antibodies. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis through a neutrophil-dependent mechanism...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28751247/modulation-of-biomarker-expression-by-osimertinib-results-of-the-paired-tumor-biopsy-cohorts-of-the-aura-phase-i-trial
#19
Kenneth S Thress, Vivien Jacobs, Helen K Angell, James Chih-Hsin Yang, Lecia V Sequist, Fiona Blackhall, Wu-Chou Su, Martin Schuler, Jürgen Wolf, Kathryn A Gold, Mireille Cantarini, J Carl Barrett, Pasi A Jänne
INTRODUCTION: Osimertinib is an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR TKI and T790M resistance mutations. To enhance understanding of osimertinib's mechanism of action, we aimed to evaluate the modulation of key molecular biomarkers after osimertinib treatment in paired clinical samples from the phase I AURA trial. METHODS: Paired tumor biopsy samples were collected before the study and after 15 plus or minus 7 days of osimertinib treatment (80 or 160 mg daily)...
July 24, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28747551/egfr-or-her2-inhibition-modulates-the-tumor-microenvironment-by-suppression-of-pd-l1-and-cytokines-release
#20
Koung Jin Suh, Ji Hea Sung, Jin Won Kim, Song-Hee Han, Hye Seung Lee, Ahrum Min, Mi Hyun Kang, Ji Eun Kim, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Seock-Ah Im, Jong Seok Lee
BACKGROUND: Characteristics of tumor microenvironment have been suggested as predictive markers of anti-EGFR or anti-HER2 treatment response. However, the effect of EGFR/HER2 signal blockade on the tumor immune microenvironment is unclear. METHODS: EGFR/HER2 pathway signaling and PD-L1 expression in gastric cancer cell lines were screened by western blot analysis. PD-L1 and HER2 expressions in 251 resected gastric tumors were determined by immunohistochemistry, and changes in EFGR, HER2, and PD-L1 expression in paired specimens between pre- and post-chemotherapy were evaluated...
July 12, 2017: Oncotarget
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