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SCLC “immune checkpoint inhibitors”

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https://www.readbyqxmd.com/read/29953115/immune-checkpoint-inhibitors-and-small-cell-lung-cancer-what-s-new
#1
REVIEW
Sabine Schmid, Martin Früh
Despite extensive research no meaningful progress in systemic treatment of small cell lung cancer (SCLC) has been made in the past decades. Earlier attempts with immunotherapy including interferon and vaccination approaches had limited success. High mutational load, smoking history and potentially also the frequent presence of paraneoplastic phenomena-indicating an activated immune system-represent a rationale for a benefit from immune checkpoint inhibitors in SCLC. However, the likelihood of response is diminished due to poor T-cell activation resulting from low expression of MHC class I antigens, low amounts of tumor infiltrating lymphocytes (TILs) and low PD-L1 expression rates...
May 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29951303/immune-related-adverse-events-with-immune-checkpoint-inhibitors-in-thoracic-malignancies-focusing-on-non-small-cell-lung-cancer-patients
#2
REVIEW
Jordi Remon, Laura Mezquita, Jesús Corral, Noelia Vilariño, Noemi Reguart
Immune checkpoint inhibitors (ICIs) have revolutionized treatment landscape among non-small cell lung cancer (NSCLC) patients in first- and second-line setting, and may become soon new treatment options in other thoracic malignancies such as small cell lung cancer (SCLC) or mesothelioma. The use of these drugs has indubitably changed the toxicity profile the oncologists are familiar with, and new spectra of immune-related adverse events are being reported with the widespread use of immunotherapies in solid tumors...
May 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29862234/advanced-small-cell-lung-cancer-sclc-new-challenges-and-new-expectations
#3
REVIEW
Nikolaos Tsoukalas, Eleni Aravantinou-Fatorou, Panagiotis Baxevanos, Maria Tolia, Konstantinos Tsapakidis, Michail Galanopoulos, Michail Liontos, George Kyrgias
Small cell lung cancer (SCLC) remains one of the most lethal malignancies and a major health riddle. The therapeutic options are limited. The combination of etoposide or irinotecan with platinum chemotherapy is the standard of care at any stage. The last decade systemic efforts have been done to reveal specific therapeutic targets for small cell lung carcinomas. In this review, we focus on the new therapeutic strategies of SCLC, including immune-related treatment that may change the prognosis of the disease...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29845250/identi%C3%AF-cation-of-candidate-biomarkers-and-pathways-associated-with-sclc-by-bioinformatics-analysis
#4
Pushuai Wen, Tungamirai Chidanguro, Zhuo Shi, Huanyu Gu, Nan Wang, Tongmei Wang, Yuhong Li, Jing Gao
Small cell lung cancer (SCLC) is one of the highly malignant tumors and a serious threat to human health. The aim of the present study was to explore the underlying molecular mechanisms of SCLC. mRNA microarray datasets GSE6044 and GSE11969 were downloaded from Gene Expression Omnibus database, and the differentially expressed genes (DEGs) between normal lung and SCLC samples were screened using GEO2R tool. Functional and pathway enrichment analyses were performed for common DEGs using the DAVID database, and the protein‑protein interaction (PPI) network of common DEGs was constructed by the STRING database and visualized with Cytoscape software...
August 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29789013/prognostic-significance-of-pd-l1-expression-and-cd8-t-cell-infiltration-in-pulmonary-neuroendocrine-tumors
#5
Haiyue Wang, Zhongwu Li, Bin Dong, Wei Sun, Xin Yang, Ruping Liu, Lixin Zhou, Xiaozheng Huang, Ling Jia, Dongmei Lin
BACKGROUND: Recent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) in pulmonary neuroendocrine tumors (PNETs) have not been fully studied. Therefore, we investigated PNETs for the expression of PD-L1 and infiltration by CD8+ TILs as well as the prognostic value of both factors. METHODS: In total, 159 specimens of PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in this study...
May 22, 2018: Diagnostic Pathology
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#6
REVIEW
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
July 1, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29731394/tumor-mutational-burden-and-efficacy-of-nivolumab-monotherapy-and-in-combination-with-ipilimumab-in-small-cell-lung-cancer
#7
Matthew D Hellmann, Margaret K Callahan, Mark M Awad, Emiliano Calvo, Paolo A Ascierto, Akin Atmaca, Naiyer A Rizvi, Fred R Hirsch, Giovanni Selvaggi, Joseph D Szustakowski, Ariella Sasson, Ryan Golhar, Patrik Vitazka, Han Chang, William J Geese, Scott J Antonia
Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer (SCLC), but predictive markers are unknown. We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonrandomized or randomized cohorts of CheckMate 032. Patients received nivolumab (3 mg/kg every 2 weeks) or nivolumab plus ipilimumab (1 mg/kg plus 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks)...
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29722737/role-of-immune-checkpoint-inhibitors-in-small-cell-lung-cancer
#8
REVIEW
Maryann R Cooper, Abdullah M Alrajhi, Cheryl R Durand
BACKGROUND: Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses each year. SCLC is characterized by a rapid doubling time, early metastatic spread, and an unfavorable prognosis overall. AREAS OF UNCERTAINTY: Most patients with SCLC will respond to initial treatment; however, the majority will experience a disease recurrence and response to second-line therapies is poor. Immune checkpoint inhibitors may be an option given the success in other diseases...
May 2018: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29593891/immune-checkpoint-inhibitors-in-small-cell-lung-cancer
#9
REVIEW
Suchita Pakkala, Taofeek K Owonikoko
Small cell lung cancer (SCLC) is a rapidly progressive cancer that often debilitates patients within months of detection and quickly becomes refractory to the limited options of therapy. While SCLC is not generally considered an immunogenic tumor, clinical experience suggests that patients with robust immune response manifesting as paraneoplastic syndrome are more likely to present with limited stage of the disease and tend to have a better prognosis. Monoclonal antibodies targeting critical negative regulators of immune response, so called immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) have expanded the application of immune-based therapies to increasing number of advanced stage cancers...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29581877/immune-checkpoint-inhibitors-in-large-cell-neuroendocrine-carcinoma-current-status
#10
Aman Chauhan, Susanne M Arnold, Jill Kolesar, Hala Elnakat Thomas, Mark Evers, Lowell Anthony
Introduction: Large cell neuroendocrine carcinomas (LCNEC) are a group of rare high grade neuroendocrine tumors that often behave clinically like small cell carcinoma (SCLC) and are treated as such. No major advancement in the management of these tumors has occurred in the last 30 years. Methods: We present a case series of three cases from Markey Cancer center along with a review of 13 published cases in the literature wherein immune-checkpoint inhibitors were utilized in the management of LCNEC...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29535912/targeting-dna-damage-repair-in-small-cell-lung-cancer-and-the-biomarker-landscape
#11
REVIEW
Triparna Sen, Carl M Gay, Lauren Averett Byers
Small cell lung cancer (SCLC) is an aggressive malignancy that accounts for 14% of all lung cancer diagnoses. Despite decades of active research, treatment options for SCLC are limited and resistance to the few Food and Drug Administration (FDA) approved therapies develops rapidly. With no approved targeted agents to date, new therapeutic strategies are desperately needed. SCLC is characterized by high mutation burden, ubiquitous loss of TP53 and RB1, mutually exclusive amplification of MYC family members, thereby, high genomic instability...
February 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29435295/identification-of-candidate-responders-for-anti-pd-l1-pd-1-immunotherapy-rova-t-therapy-or-ezh2-inhibitory-therapy-in-small-cell-lung-cancer
#12
Motonobu Saito, Katsuharu Saito, Kouya Shiraishi, Daichi Maeda, Hiroyuki Suzuki, Yoshihiro Minamiya, Koji Kono, Takashi Kohno, Akiteru Goto
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#13
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of NSCLC underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival both in unselected pretreated patients and in untreated patients with programmed death ligand 1 expression of 50% or more. Furthermore, compelling preliminary results were reported for new combinations of anti-programmed cell death 1/programmed death ligand 1 agents with chemotherapy or anti-cytotoxic T-lymphocyte associated protein 4 inhibitors...
March 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29318609/the-efficacy-and-safety-of-anti-pd-1-pd-l1-antibodies-combined-with-chemotherapy-or-ctla4-antibody-as-a-first-line-treatment-for-advanced-lung-cancer
#14
Xiaoling Xu, Zhiyu Huang, Lei Zheng, Yun Fan
Checkpoint inhibitors show promising efficacy in advanced lung cancer, especially in non-small-cell lung cancer (NSCLC). This meta-analysis was conducted to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as first-line treatments for patients with advanced lung cancer. A systematic search was performed in databases for this system review and quantitative meta-analysis. Twelve trials were finally enrolled in the meta-analysis. Our analyses revealed that the combined overall response rate (ORR) and disease control rate (DCR) for immune checkpoint inhibitors combined with chemotherapy for the treatment of NSCLC were 47...
June 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29302251/immunotherapy-for-non-small-cell-lung-cancer-current-status-and-future-obstacles
#15
REVIEW
Ju Hwan Cho
Lung cancer is one of the leading causes of death worldwide. There are 2 major subtypes of lung cancer, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Studies show that NSCLC is the more prevalent type of lung cancer that accounts for approximately 80%-85% of cases. Although, various treatment methods, such as chemotherapy, surgery, and radiation therapy have been used to treat lung cancer patients, there is an emergent need to develop more effective approaches to deal with advanced stages of tumors...
December 2017: Immune Network
https://www.readbyqxmd.com/read/28935016/-clinical-development-of-immune-checkpoint-inhibitors-in-patients-with-small-cell-lung-cancer
#16
REVIEW
Shuang Zhang, Jingjing Liu, Ying Cheng
Small cell lung cancer (SCLC) is a poorly differentiated high-grade neuroendocrine tumor, accounts for approximately 14% of all lung cancers. SCLC is characterized by rapid growth, early metastasis without effective treatments after recurrence. It is urgently need to improve the therapy of patients with SCLC. In recent years Tumor immunotherapy has shown promising efficacy, especially in immune checkpoints including inhibitors programmed cell-death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)...
September 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28579387/treatment-advances-in-small-cell-lung-cancer-sclc
#17
REVIEW
Saiama N Waqar, Daniel Morgensztern
Small cell lung cancer (SCLC) is an aggressive tumor characterized by rapid doubling time and high propensity for early development of disseminated disease. Although most patients respond to initial therapy with a platinum doublet, the majority of those with limited stage and virtually all patients with metastatic disease eventually develop tumor progression for which there are limited treatment options. There have been no recent changes in the treatment of SCLC, with platinum plus etoposide and topotecan as the standard first-line and second-line respectively, neither showing survival benefit over the combination of cyclophosphamide, doxorubicin and vincristine, which was developed in the 1970s...
December 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28536345/viroimmunotherapy-of-thoracic-cancers
#18
REVIEW
Alexander S Dash, Manish R Patel
Thoracic cancers, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and malignant pleural mesothelioma (MM), cause the highest rate of cancer mortality worldwide. Most of these deaths are as a result of NSCLC; however, prognoses for the other two diseases remain as some of the poorest of any cancers. Recent advances in immunotherapy, specifically immune checkpoint inhibitors, have begun to help a small population of patients with advanced lung cancer. People who respond to these immune therapies generally have a durable response and many see dramatic decreases in their disease...
January 4, 2017: Biomedicines
https://www.readbyqxmd.com/read/28482670/immune-checkpoint-inhibitors-in-lung-cancer-current-status-and-future-directions
#19
REVIEW
Yun Fan, Weimin Mao
Recently, the immune checkpoint inhibitors that target programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) have made a breakthrough in treating advanced non-small cell lung cancer (NSCLC) with the efficacy of approximately 20%; among which, nivolumab has acquired treatment indications in lung squamous cell carcinoma. The inhibitors targeting cytotoxic T lymphocyte associated antigen 4 (CTLA-4) are also undergoing clinical trials. Researches on immune checkpoint inhibitors have been rapidly implemented in a variety of different types of lung cancer, such as small cell lung cancer (SCLC) and locally advanced NSCLC, and these inhibitors began to be applied in combination with some established treatments, including chemotherapy, targeting therapy and radiotherapy...
April 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28064556/pd-1-checkpoint-blockade-alone-or-combined-pd-1-and-ctla-4-blockade-as-immunotherapy-for-lung-cancer
#20
REVIEW
Tawee Tanvetyanon, Jhanelle E Gray, Scott J Antonia
Signaling through T-cell surface, an immune checkpoint protein such as PD-1 or CTLA-4 helps dampen or terminate unwanted immune responses. Blocking a single immune checkpoint or multiple checkpoints simultaneously can generate anti-tumor activity against a variety of cancers including lung cancer. Area covered: This review highlights the results of recent clinical studies of single or combination checkpoint inhibitor immunotherapy in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). The authors discuss pembrolizumab and pembrolizumab plus ipilimumab, durvalumab and durvalumab plus tremelimumab, nivolumab and nivolumab plus ipilimumab for NSCLC as well as nivolumab and nivolumab plus ipilimumab for SCLC...
March 2017: Expert Opinion on Biological Therapy
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