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https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#1
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29325268/-clinical-significance-of-targeting-drug-based-molecular-biomarkers-expression-in-ovarian-clear-cell-carcinoma
#2
M J Li, H R Li, X Cheng, R Bi, X Y Tu, F Liu, L H Chen
Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues...
December 25, 2017: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/29324814/comprehensive-molecular-profiling-of-advanced-metastatic-olfactory-neuroblastomas
#3
Jasmina Topcagic, Rebecca Feldman, Anatole Ghazalpour, Jeffrey Swensen, Zoran Gatalica, Semir Vranic
Olfactory neuroblastoma (ONB) is a rare, locally aggressive, malignant neoplasm originating in the olfactory epithelium in the nasal vault. The recurrence rate of ONB remains high and there are no specific treatment guidelines for recurrent/metastatic ONBs. This study retrospectively evaluated 23 ONB samples profiled at Caris Life Sciences (Phoenix, Arizona) using DNA sequencing (Sanger/NGS [Illumina], n = 15) and gene fusions (Archer FusionPlex, n = 6), whole genome RNA microarray (HumanHT-12 v4 beadChip, Illumina, n = 4), gene copy number assays (chromogenic and fluorescent in situ hybridization), and immunohistochemistry...
2018: PloS One
https://www.readbyqxmd.com/read/29296194/changes-in-pd-l1-expression-according-to-tumor-infiltrating-lymphocytes-of-acquired-egfr-tki-resistant-egfr-mutant-non-small-cell-lung-cancer
#4
Tae-Jung Kim, Soon Auck Hong, Okran Kim, Seung Joon Kim, Ji-Hyun Yang, Eun Kyo Joung, Jin-Hyoung Kang, Sook-Hee Hong
Backgrounds: EGFR-mutant non-small cell lung cancer (NSCLC) that developed acquired resistance to EGFR-tyrosine kinase (TKI) are potential candidates for programmed death 1 (PD1) inhibitor. Results: TPS≥1% for PD-L1 and low CD8 + TIL in post-TKI tumor showed a trend for a lower PFS of EGFR-TKIs (14.2 vs 9.9 months; P = 0.060) (cohort A). Only 2 of 22 specimens (9.1%) with an acquired EGFR exon 20 T790M mutation exhibited in post-TKI TPS≥50% for PD-L1. The degree in post-TKI tumor of PD-L1 expression was varied in 19 patients (40...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295721/down-regulation-of-microrna-135-promotes-sensitivity-of-non-small-cell-lung-cancer-to-gefitinib-by-targeting-trim16
#5
Ning Wang, Tingting Zhang
Personalized treatment targeting epidermal growth factor receptor (EGFR) becomes a promising way for treatment of non-small cell lung cancer (NSCLC). Gefitinib, a tyrosine kinases inhibitor, is the first drug for NSCLC, which easily leads to drug resistance. Our study was aimed to explore the functional role of microRNA (miR)-135 in the sensitivity to gefitinib of NSCLC cells. Expression of miR-135 in normal cells and NSCLC cells was assessed. Then, the effects of abnormally expressed miR-135 on cell viability, migration, invasion, apoptosis, sensitivity to gefitinib, and the expression levels of adhesion molecules and programmed death ligand 1 (PD-L1) were all analyzed in H1650 and H1975 cells...
January 2, 2018: Oncology Research
https://www.readbyqxmd.com/read/29290777/classifying-non-small-cell-lung-cancer-by-status-of-programmed-cell-death-ligand-1-and-tumor-infiltrating-lymphocytes-on-tumor-cells
#6
Shaohua Cui, Lili Dong, Jialin Qian, Lin Ye, Liyan Jiang
Purpose: To explore the possible correlation between programmed death ligand 1 (PD-L1)/tumor-infiltrating lymphocytes (TIL) status and clinical factors in non-small cell lung (NSCLC). Materials and Methods: A total of 126 surgical NSCLC samples with stage I to IIIA were retrospectively collected and analyzed. Immunohistochemistry (IHC) assays were used to detect PD-L1 protein expression. PD-L1 positivity on tumor cells was defined by positive tumor cell (TC) percentage using 5% cutoff value. Results: Thirty-seven patients (29...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29290263/abundant-tumor-promoting-stromal-cells-in-lung-adenocarcinoma-with-hypoxic-regions
#7
Hiroshi Nakamura, Tomohiro Ichikawa, Shoko Nakasone, Tomohiro Miyoshi, Masato Sugano, Motohiro Kojima, Satoshi Fujii, Atsushi Ochiai, Takeshi Kuwata, Keiju Aokage, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii
OBJECTIVES: Carbonic anhydrase IX (CAIX) is a marker of hypoxia and its expression by cancer associated fibroblasts (CAFs) was reportedly associated with the poor prognosis of lung adenocarcinoma. This study aimed to characterize the hypoxic microenvironment containing CAIX (+) CAFs. MATERIALS AND METHODS: First, we evaluated the clinicopathological significance of CAIX expression by CAFs in 3cm and above lung adenocarcinoma (n=188). We then compared the expressions of E-cadherin, ezrin, ALDH-1, CD44, EGFR, HSF-1, Glut-1, and PD-L1 in cancer cells, as well as those of CD204 and podoplanin in stromal cells between CAIX (+) CAFs and CAIX (-) CAFs cases (n=25, each)...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29290252/immune-checkpoint-inhibitors-in-epidermal-growth-factor-receptor-mutant-non-small-cell-lung-cancer-current-controversies-and-future-directions
#8
REVIEW
Ross A Soo, Sun Min Lim, Nicholas L Syn, Rebecca Teng, Richie Soong, Tony S K Mok, Byoung Chul Cho
Major advances with the development of epidermal growth factor receptor tyrosine kinase inhibitors and immune check-point inhibitors have ushered in a new era in lung cancer therapy. Whilst pre-clinical studies suggest EGFR-driven NSCLC inhibit antitumor immunity through the activation of the PD-1/PD-L1 pathway, epidemiology studies suggest EGFR mutant NSCLC are more likely to have decreased PD-L1 expression. The superiority of single agent PD-1/PD-L1 inhibitors over docetaxel in pre-treated EGFR mutant NSCLC appears to be moderated...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29251665/molecular-pathology-of-lung-cancer-current-status-and-perspectives
#9
Felicitas Oberndorfer, Leonhard Müllauer
PURPOSE OF REVIEW: In this article, we summarize the current knowledge on molecular alterations in lung cancer that are targets for therapy, and provide an outlook on the future development of molecular pathology in precision oncology. RECENT FINDINGS: Lung cancer has become a paradigm for the success of molecular targeted therapies in solid tumors. Tyrosine kinase inhibitors are effective treatment options in adenocarcinoma patients with an EGFR, ALK, ROS1 or B-Raf Proto-Oncogene, Serine/Threonine kinase mutation...
December 14, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29246028/challenges-and-future-of-biomarker-tests-in-the-era-of-precision-oncology-can-we-rely-on-immunohistochemistry-ihc-or-fluorescence-in-situ-hybridization-fish-to-select-the-optimal-patients-for-matched-therapy
#10
REVIEW
Young Kwang Chae, Ayush Arya, Lauren Chiec, Hiral Shah, Ari Rosenberg, Sandip Patel, Kirtee Raparia, Jaehyuk Choi, Derek A Wainwright, Victoria Villaflor, Massimo Cristofanilli, Francis Giles
Molecular techniques have improved our understanding of the pathogenesis of cancer development. These techniques have also fueled the rational development of targeted drugs for patient populations stratified by their genetic characteristics. These novel methods have changed the classic paradigm of diagnostic pathology; among them are IHC, FISH, polymerase chain reaction (PCR) and microarray technology. IHC and FISH detection methods for human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR) and programmed death ligand-1 (PD-L1) were recently approved by the Food and Drug Administration (FDA) as routine clinical practice for cancer patients...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29239193/-checkpoint-inhibitors-in-the-treatment-of-upper-gastrointestinal-tract-tumors
#11
R Obermannova
Chemotherapy prolongs overall survival (OS) in esophageal (EC) and gastric cancer (GC). Unsatisfactory results of systemic therapy initiated a search for new treatment options. In metastatic disease, a number of targeted drugs were tested; however, several phase III studies assessing receptor tyrosin kinase-related signaling pathways, such as EGFR, MET/HGF or mTOR, failed. Trastuzumab remains the only targeted drug with a known molecular predictor, which extended the OS in metastatic gastric adenocarcinoma and adenocarcinoma of esophago-gastric junction...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29238224/prognostic-value-of-cox-2-and-pd-l1-expression-and-its-relationship-with-tumor-infiltrating-lymphocytes-in-resected-lung-adenocarcinoma
#12
Katsuhiko Shimizu, Riki Okita, Shinsuke Saisho, Ai Maeda, Yuji Nojima, Masao Nakata
Programmed cell death-1 ligand 1 (PD-L1), tumor-infiltrating CD8-positive T lymphocytes (CD8-positive TILs), and cyclooxygenase-2 (Cox-2) have been used as prognostic tools in patients with lung adenocarcinoma. We conducted a retrospective review of data from 170 patients who had undergone pulmonary resection as an initial treatment for clinical T1-2 N0 lung adenocarcinoma. We then investigated the expressions of three biomarkers using immunohistochemical analyses and compared the expression levels with the clinicopathological characteristics and outcomes of the patients...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/29228652/clinical-characteristics-and-programmed-cell-death-ligand-1-expression-in-adenocarcinoma-in-situ-and-minimally-invasive-adenocarcinoma-of-lung
#13
Renke Yu, Zhengfu He, Ying Lou, Hanliang Jiang, Yuhui Wu, Zhen Liu, Hongming Pan, Weidong Han
Objectives: According to the IASLC/ATS/ERS 2011 classification, there are two new conceptions of lung adenocarcinoma, adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), which are very early stages of lung adenocarcinoma. This study aimed to analyze clinical features of AIS and MIA and determine the expression profile of PD-L1 in AIS and MIA. Results: In all 274 patients, 77 were diagnosed as AIS and 197 as MIA. We accidentally found 4 patients with recurrence, which were all MIA...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227119/-molecular-pathology-of-lung-cancer-in-routine-diagnostic-practice-2017-update
#14
Radoslav Matěj, Zdeněk Rohan, Kristýna Němejcová, Pavel Dundr
The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Analysis of EGFR gene mutations and ALK rearrangement in lung adenocarcinomas are already routinely performed and are closely related to the indication for the administration of tyrosinkinase inhibitors...
2017: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/29225694/non-small-cell-lung-cancer-treatment-r-evolution-ten-years-of-advances-and-more-to-come
#15
REVIEW
Luca Toschi, Sabrina Rossi, Giovanna Finocchiaro, Armando Santoro
Diagnostic and treatment algorithms in non-small cell lung cancer (NSCLC) are evolving at a never-before-seen pace. Histological subtyping to maximise treatment efficacy and avoid toxicity has marked the beginning of the revolution, opening the way to molecular characterisation to guide genomically driven treatments with targeted agents, led by Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) inhibitors. More recently, agents against the Program Death 1 receptor (PD-1) and ligand 1 (PD-L1) have entered the clinical arena, offering new hope to NSCLC patients, although several uncertainties remain to be elucidated...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/29214427/characterization-of-pd-l1-expression-in-chinese-non-small-cell-lung-cancer-patients-with-pten-expression-as-a-means-for-tissue-quality-screening
#16
Xu-Chao Zhang, Xu Cao, Chun Sun, Zhi Xie, Jian-Jun Guo, Jin-Ji Yang, Xue-Ning Yang, Hang-Jun Dai, Su-Chun Li, Xin-Ran Xu, Yun-Xia Zuo, Meng Chen, Hartmut Koeppen, Jing He, Astrid Kiermaier, David Shames, Gang Cheng, Yi-Long Wu
The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay...
December 6, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29212184/cordycepin-and-a-preparation-from-cordyceps-militaris-inhibit-malignant-transformation-and-proliferation-by-decreasing-egfr-and-il-17ra-signaling-in-a-murine-oral-cancer-model
#17
Peng-Yang Hsu, Yueh-Hsin Lin, Erh-Ling Yeh, Hui-Chen Lo, Tai-Hao Hsu, Che-Chun Su
Cordyceps militaris (CM) and its active ingredient cordycepin have been reported to inhibit tumor growth, but the mechanisms are not fully understood. This study used a mouse model for oral cancer and a cell line, 4NAOC-1 derived from the model to study the mechanisms. Our results show that a CM preparation (CMP) can significantly inhibit tumor development and malignant transformation in the model. In vitro data indicate that CMP and cordycepin can inhibit 4NAOC-1 cell proliferation, either anchorage-dependent or -independent...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203588/spatially-resolved-and-quantitative-analysis-of-vista-pd-1h-as-a-novel-immunotherapy-target-in-human-non-small-cell-lung-cancer
#18
Franz Villarroel-Espindola, Xiaoqing Yu, Ila Datar, Nikita Mani, Miguel F Sanmamed, Vamsidhar Velcheti, Konstantinos N Syrigos, Maria I Toki, Hongyu Zhao, Lieping Chen, Roy S Herbst, Kurt A Schalper
PURPOSE: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human NSCLC. EXPERIMENTAL DESIGN: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1 and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T-cells, CD4+ T-helper cells, CD8+ cytotoxic T-cells, CD20+ B-lymphocytes and CD68+ tumor-associated macrophages...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29191596/pd-l1-expression-in-advanced-nsclc-insights-into-risk-stratification-and-treatment-selection-from-a-systematic-literature-review
#19
REVIEW
Robert Brody, Yiduo Zhang, Marc Ballas, Mohd Kashif Siddiqui, Palvi Gupta, Craig Barker, Anita Midha, Jill Walker
Tumors can evade immune detection by exploiting inhibitory immune checkpoints such as the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Antibodies that block this pathway offer a promising new approach to treatment in advanced/metastatic non-small cell lung cancer (NSCLC). A systematic review of the literature was conducted to assess the association of PD-L1 with important patient and disease characteristics, the prognostic significance of PD-L1 expressing NSCLC tumors, and the value of PD-L1 as a predictive biomarker of response to anti-PD-1/PD-L1 treatments in advanced/metastatic NSCLC...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29184782/beyond-chemotherapy-for-advanced-disease-the-role-of-egfr-and-pd-1-inhibitors
#20
REVIEW
Weijie Gu, Yao Zhu, Dingwei Ye
Penile squamous cell carcinoma (SCC) is a rare malignancy with limited treatment options when the tumor is unresectable and/or chemorefractory. Triplet systemic chemotherapy regimens including taxane and cisplatin are recommended, but the response duration can be short and the treatment-related toxicity high. Only a small proportion of patients survive 1 year or longer with the current standard treatment paradigm. Beyond chemotherapy, the use of novel targeted agents, either alone or in combination with traditional chemotherapeutic agents, has appeared to have promising efficacy in patients with platinum-refractory penile cancer...
October 2017: Translational Andrology and Urology
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