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https://www.readbyqxmd.com/read/29155348/progress-and-challenges-of-predictive-biomarkers-of-anti-pd-1-pd-l1-immunotherapy-a-systematic-review
#1
Feifei Teng, Xiangjiao Meng, Li Kong, Jinming Yu
Despite the marked success of applications of PD-1/PD-L1 checkpoint blockades in clinical, the efficacy and responsiveness of these agents varies greatly among different tumor types and across individual patients. Therefore, establishment of predictive biomarkers for checkpoint blockades is of the most importance to maximize the therapeutic benefits. In this review, we discuss the current progress and challenges of developing predictive biomarkers of immunotherapy responsiveness, aiming to provide some directions for future studies...
November 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29152077/concordance-of-programmed-death-ligand-1-expression-between-primary-and-metastatic-non-small-cell-lung-cancer-by-immunohistochemistry-and-rna-in-situ-hybridization
#2
Hye Ryun Kim, Yoon Jin Cha, Min Hee Hong, Manoj Gandhi, Shauna Levinson, Inkyung Jung, Jin Gu Lee, Chang Young Lee, Byoung Chul Cho, Sang-Jun Ha, Hyo Sup Shim
We investigated the concordance of programmed death-ligand 1 (PD-L1) expression between primary cancer at initial diagnosis and metastasis at recurrence in resected non-small cell lung cancer (NSCLC). PD-L1 expression was evaluated using the SP142 assay in 37 NSCLC patients with paired primary lung cancer and surgically resected metastases at recurrence. PD-L1 positivity was defined as immunohistochemistry (IHC) and also evaluated by RNA in situ hybridization (RISH). The concordance rate of PD-L1 between primaries and metastases and correlation with clinicopathological factors were analyzed...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147605/egfr-mutation-correlates-with-uninflamed-phenotype-and-weak-immunogenicity-causing-impaired-response-to-pd-1-blockade-in-non-small-cell-lung-cancer
#3
Zhong-Yi Dong, Jia-Tao Zhang, Si-Yang Liu, Jian Su, Chao Zhang, Zhi Xie, Qing Zhou, Hai-Yan Tu, Chong-Rui Xu, Li-Xu Yan, Yu-Fa Li, Wen-Zhao Zhong, Yi-Long Wu
Patients with EGFR mutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association between EGFR mutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation between EGFR mutation and PD-L1 expression, and the association of EGFR status with response to anti-PD-1/L1 therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29140105/durvalumab-in-non-small-cell-lung-cancer-patients-current-developments
#4
Laura Mezquita, David Planchard
Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population. Durvalumab is under evaluation in early, locally advanced and advanced disease as monotherapy and combined with ICIs, targeted therapies, chemotherapy and radiotherapy...
November 15, 2017: Future Oncology
https://www.readbyqxmd.com/read/29119113/increased-egfr-phosphorylation-correlates-with-higher-programmed-death-ligand-1-expression-analysis-of-tki-resistant-lung-cancer-cell-lines
#5
Kenichi Suda, Leslie Rozeboom, Koh Furugaki, Hui Yu, Mary Ann C Melnick, Kim Ellison, Christopher J Rivard, Katerina Politi, Tetsuya Mitsudomi, Fred R Hirsch
Despite the recent development of immunotherapies that target programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) treatment, these therapies are less effective in NSCLC patients with epidermal growth factor receptor (EGFR) mutations. However, the molecular mechanisms underlying this lower efficacy of immunotherapies in EGFR mutant lung cancers are still unclear. In this study, we analyzed PD-L1 protein expression in lung cancer cell lines with EGFR mutations prior to and after acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29114472/molecular-diagnostics-of-lung-cancer-in-the-clinic
#6
REVIEW
Lynette Sholl
According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor (EGFR) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively...
October 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29113454/modulators-of-redox-metabolism-in-head-and-neck-cancer
#7
Xiaofei Chen, Jade Mims, Xiumei Huang, Naveen Singh, Edward A Motea, Sarah M Planchon, Muhammad Beg, Allen W Tsang, Mercedes Porosnicu, Melissa L Kemp, David A Boothman, Cristina Furdui
SIGNIFICANCE: Head and Neck Squamous Cell Cancer (HNSCC) is a complex disease characterized by high genetic and metabolic heterogeneity. Radiation therapy (RT) alone or combined with systemic chemotherapy is widely used for treatment of HNSCC as definitive treatment or as adjuvant treatment after surgery. Antibodies against Epidermal Growth Factor Receptor (EGFR) are used in definitive or palliative treatment. Recent Advances. Emerging targeted therapies against other proteins of interest as well as programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) immunotherapies are being explored in clinical trials...
November 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29110857/inter-relationship-between-pd-l1-expression-and-clinic-pathological-features-and-driver-gene-mutations-in-pulmonary-sarcomatoid-carcinomas
#8
Filippo Lococo, Federica Torricelli, Giulio Rossi, Marco Alifano, Diane Damotte, Cristian Rapicetta, Ione Tamagnini, Alberto Cavazza, Simonetta Piana, Carla Galeone, Massimiliano Paci, Alessia Ciarrocchi
INTRODUCTION: Pulmonary Sarcomatoid Carcinoma (PSC) is a rare subset of NSCLC, associated with worse prognosis and resistant to platinum-based regimens. Recent investigations have shown high levels of PD-L1 expression in PSC, providing a rationale for the potential use of immunotherapy. In this study, we investigated whether the PD-L1 expression was related to clinico-pathologic and molecular characteristics. MATERIALS AND METHODS: Fortythree surgically-resected PSCs were selected from 2006 to 2014 and clinical information retrieved...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29094049/diagnostic-predictive-prognostic-and-therapeutic-molecular-biomarkers-in-third-millennium-a-breakthrough-in-gastric-cancer
#9
REVIEW
Nicola Carlomagno, Paola Incollingo, Vincenzo Tammaro, Gaia Peluso, Niccolò Rupealta, Gaetano Chiacchio, Maria Laura Sandoval Sotelo, Gianluca Minieri, Antonio Pisani, Eleonora Riccio, Massimo Sabbatini, Umberto Marcello Bracale, Armando Calogero, Concetta Anna Dodaro, Michele Santangelo
Introduction: Gastric cancer is the fifth most common cancer and the third cause of cancer death. The clinical outcomes of the patients are still not encouraging with a low rate of 5 years' survival. Often the disease is diagnosed at advanced stages and this obviously negatively affects patients outcomes. A deep understanding of molecular basis of gastric cancer can lead to the identification of diagnostic, predictive, prognostic, and therapeutic biomarkers. Main Body: This paper aims to give a global view on the molecular classification and mechanisms involved in the development of the tumour and on the biomarkers for gastric cancer...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29074606/low-pd-1-expression-in-cytotoxic-cd8-tumor-infiltrating-lymphocytes-confers-an-immune-privileged-tissue-microenvironment-in-nsclc-with-a-prognostic-and-predictive-value
#10
Giulia Mazzaschi, Denise Madeddu, Angela Falco, Giovanni Bocchialini, Matteo Goldoni, Francesco Sogni, Giovanna Armani, Costanza Annamaria Lagrasta, Bruno Lorusso, Chiara Maria Mangiaracina, Rocchina Vilella, Caterina Frati, Roberta R Alfieri, Luca Ampollini, Michele Veneziani, Enrico M Silini, Andrea Ardizzoni, Konrad Urbanek, Franco Aversa, Federico Quaini, Marcello Tiseo
The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially impact on clinical outcome in Non Small Cell Lung Cancer (NSCLC), an extended analysis of PD-L1 and Tumor Infiltrating Lymphocytes (TILs) was performed. Experimental Design Samples from resected adenocarcinoma (ADC 42) and squamous cell carcinoma (SCC 58) and from 26 advanced diseases (13 ADC, 13 SCC) treated with nivolumab were analyzed...
October 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#11
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29036791/globo-h-expression-is-associated-with-driver-mutations-and-pd-l1-expressions-in-stage-i-non-small-cell-lung-cancer
#12
Ching-Yao Yang, Mong-Wei Lin, Yih-Leong Chang, Chen-Tu Wu
BACKGROUND: Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. OBJECTIVES: We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1)...
September 29, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29029530/which-treatment-is-preferred-for-advanced-non-small-cell-lung-cancer-with-wild-type-epidermal-growth-factor-receptor-in-second-line-therapy-a-meta-analysis-comparing-immune-checkpoint-inhibitor-tyrosine-kinase-inhibitor-and-chemotherapy
#13
Di Wu, Chongyang Duan, Fenfang Wu, Liyong Chen, Size Chen
BACKGROUND: The recommendations regarding the optimum treatment for advanced non-small-cell lung cancer (NSCLC) patients with wild-type (WT) epidermal growth factor receptor (EGFR) tumors remain unclear. This meta-analysis was conducted to assess the efficacy among programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) antibody, EGFR-tyrosine kinase inhibitors (TKI) and chemotherapy in second-and third-line therapy. PATIENTS AND METHODS: Randomized trials investigating two of the three treatments were searched and included...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969070/immunohistochemical-assays-incorporating-sp142-and-22c3-monoclonal-antibodies-for-detection-of-pd-l1-expression-in-nsclc-patients-with-known-status-of-egfr-and-alk-genes
#14
Paweł Krawczyk, Bożena Jarosz, Tomasz Kucharczyk, Anna Grenda, Katarzyna Reszka, Juliusz Pankowski, Kamila Wojas-Krawczyk, Marcin Nicoś, Justyna Szumiło, Tomasz Trojanowski, Janusz Milanowski
Different immunohistochemical (IHC) assays were approved for PD-L1 expression examination on tumor cells in qualification to immune-checkpoint inhibitors therapy in NSCLC patients. These assays have some similarities, but also very serious differences. We assessed 2 IHC tests for PD-L1 expression evaluation in NSCLC tumors with different pathological diagnoses and genetic abnormalities. We enrolled 48 NSCLC patients (median age: 65 years) with known status of EGFR and ALK genes. We compared the effectiveness of PD-L1 expression examination of two IHC assays with 22C3 (Dako) and SP142 antibodies (Ventana)...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969039/egfr-or-her2-inhibition-modulates-the-tumor-microenvironment-by-suppression-of-pd-l1-and-cytokines-release
#15
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...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932563/a-systematic-and-genome-wide-correlation-meta-analysis-of-pd-l1-expression-and-targetable-nsclc-driver-genes
#16
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
#17
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
#18
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
#19
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
#20
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
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