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Lung Cancer: Targets and Therapy

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https://www.readbyqxmd.com/read/29844707/response-to-rapamycin-analogs-but-not-pd-1-inhibitors-in-pten-mutated-metastatic-non-small-cell-lung-cancer-with-high-tumor-mutational-burden
#1
Ankur R Parikh, Siraj M Ali, Alexa B Schrock, Lee A Albacker, Vincent A Miller, Phil J Stephens, Pamela Crilley, Maurie Markman
In non-small-cell lung cancer (NSCLC) refractory to standard therapy and which lacks well-known oncogenic drivers, genomic profiling can still identify genomic alterations that may suggest potential sensitivity to targeted therapy. PTEN mutation in NSCLC may be sensitizing to analogs of rapamycin such as everolimus or temsirolimus, but more investigation is needed. We report the case of a patient with metastatic NSCLC harboring a PTEN mutation as well as high tumor mutational burden and PD-L1 positivity with a durable response to temsirolimus, but refractory to a checkpoint inhibitor...
2018: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29628779/role-and-inhibition-of-gli1-protein-in-cancer
#2
REVIEW
Eloise Mastrangelo, Mario Milani
GLI1 is a transcriptional regulator involved in the development of different types of cancer. GLI1 transcriptional activity is regulated within the Hedgehog pathway (canonical activity), but can also be controlled independently (non-canonical activity) in the context of other signaling pathways. Experimental evidences show GLI1 involvement in both small- and non-small-cell lung cancers. Direct inhibition of the protein, in combination with other chemotherapeutic agents, represents a promising strategy for the treatment of different malignancies...
2018: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29615847/uncommon-egfr-mutations-in-cytological-specimens-of-1-874-newly-diagnosed-indonesian-lung-cancer-patients
#3
Elisna Syahruddin, Laksmi Wulandari, Nunuk Sri Muktiati, Ana Rima, Noni Soeroso, Sabrina Ermayanti, Michael Levi, Heriawaty Hidajat, Grace Widjajahakim, Ahmad Rusdan Handoyo Utomo
Purpose: We aimed to evaluate the distribution of individual epidermal growth factor receptor ( EGFR ) mutation subtypes found in routine cytological specimens. Patients and methods: A retrospective audit was performed on EGFR testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015-2016). Testing was performed by ISO15189 accredited central laboratory. Results: Overall test failure rate was 5...
2018: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29588624/stereotactic-body-radiation-therapy-sbrt-in-the-management-of-non-small-cell-lung-cancer-clinical-impact-and-patient-perspectives
#4
REVIEW
Elysia K Donovan, Anand Swaminath
Stereotactic body radiation therapy (SBRT) has emerged as a new technology in radiotherapy delivery, allowing for potentially curative treatment in many patients previously felt not to be candidates for radical surgical resection of stage I non-small-cell lung cancer (NSCLC). Several studies have demonstrated very high local control rates using SBRT, and more recent data have suggested overall survival may approach that of surgery in operable patients. However, SBRT is not without unique toxicities, and the balance of toxicity, and effect on patient-reported quality of life need to be considered with respect to oncologic outcomes...
2018: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29379323/validation-of-liquid-biopsy-plasma-cell-free-dna-testing-in-clinical-management-of-advanced-non-small-cell-lung-cancer
#5
Vidya H Veldore, Anuradha Choughule, Tejaswi Routhu, Nitin Mandloi, Vanita Noronha, Amit Joshi, Amit Dutt, Ravi Gupta, Ramprasad Vedam, Kumar Prabhash
Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for EGFR testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung cancer (NSCLC). A total of 163 NSCLC cases were included in the validation, of which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA using deep sequencing with custom designed bioinformatics methods that could detect somatic mutations at allele frequencies as low as 0...
2018: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29276417/bevacizumab-in-the-treatment-of-nsclc-patient-selection-and-perspectives
#6
REVIEW
Alessia E Russo, Domenico Priolo, Giovanna Antonelli, Massimo Libra, James A McCubrey, Francesco Ferraù
Non-small-cell lung cancer (NSCLC) represents about 85% of all lung cancers, and more than half of NSCLCs are diagnosed at an advanced stage. Chemotherapy has reached a plateau in the overall survival curve of about 10 months. Therefore, in last decade novel targeted approaches have been developed to extend survival of these patients, including antiangiogenic treatment. Vascular endothelial growth factor (VEGF) signaling pathway plays a dominant role in stimulating angiogenesis, which is the main process promoting tumor growth and metastasis...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29263709/pretreatment-glasgow-prognostic-score-and-prognostic-nutritional-index-predict-overall-survival-of-patients-with-advanced-small-cell-lung-cancer
#7
Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta
Background: Various biomarkers have been shown to predict prognosis in various types of cancers. However, these biomarkers have not been studied in advanced small cell lung cancer (SCLC). The modified Glasgow prognostic score (mGPS) is based on serum albumin level and C-reactive protein (CRP). The prognostic nutritional index (PNI) is a combination of serum albumin level and absolute lymphocyte count. This study aimed to evaluate the prognostic value of mGPS and PNI in SCLC. Methods: We retrospectively reviewed and calculated mGPS and PNI for patients with stage IIIB or IV SCLC who initiated platinum-based combination chemotherapy between November 2007 and June 2016...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29255376/cis-oriented-solvent-front-egfr-g796s-mutation-in-tissue-and-ctdna-in-a-patient-progressing-on-osimertinib-a-case-report-and-review-of-the-literature
#8
Samuel J Klempner, Pareen Mehta, Alexa B Schrock, Siraj M Ali, Sai-Hong Ignatius Ou
Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is a universal event and limits clinical efficacy. The third-generation EGFR inhibitor osimertinib is active in EGFR-mutant/T790M positive non-small-cell lung cancer. Mechanisms of acquired resistance are emerging, and here we describe a cis-oriented solvent-front EGFR G796S mutation as the resistance mechanism observed in a progression biopsy and circulating tumor DNA (ctDNA) from a patient with initial response followed by progression on osimertinib...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29238236/pro-gastrin-releasing-peptide-progrp-as-a-biomarker-in-small-cell-lung-cancer-diagnosis-monitoring-and-evaluation-of-treatment-response
#9
REVIEW
Ewa Wojcik, Jan Kanty Kulpa
Lung cancer belongs to malignant tumors that possess the highest rates of morbidity and mortality in the world. A number of morphological, biological and clinical features justify the distinction of small-cell carcinoma with respect to the other histological types of lung cancer. The predominant neuroendocrine phenotype is critical for the selection of biomarkers used in diagnostics, monitoring and evaluation of treatment response; early onset relapses in patients with small-cell lung cancer (SCLC) and the evaluation of their prognosis...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29158696/65plus-open-label-study-of-bevacizumab-in-combination-with-pemetrexed-or-pemetrexed-carboplatin-as-first-line-treatment-of-patients-with-advanced-or-recurrent-nonsquamous-non-small-cell-lung-cancer
#10
Wolfgang Schuette, Claus-Peter Schneider, Walburga Engel-Riedel, Christian Schumann, Martin Kohlhaeufl, Monika Heidi Ursel Serke, Gert Hoeffken, Cornelius Kortsik, Martin Reck
Background: The aim of the study was to investigate in terms of noninferiority the efficacy and safety of a monochemotherapy regimen of pemetrexed plus bevacizumab (BevPem) versus carboplatin/pemetrexed plus bevacizumab (BevCPem) in elderly patients as first-line treatment for advanced metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC). Materials and methods: 65Plus was a Phase III, randomized, open-label study. In total, 253 patients received BevPem (n=119) or BevCPem (n=134)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29138610/-nab-paclitaxel-carboplatin-induction-in-squamous-nsclc-longitudinal-quality-of-life-while-on-chemotherapy
#11
Michael Thomas, David R Spigel, Robert M Jotte, Michael McCleod, Mark A Socinski, Ray D Page, Laurent Gressot, Jeanna Knoble, Oscar Juan, Daniel Morgensztern, Dolores Isla, Edward S Kim, Howard West, Amy Ko, Teng Jin Ong, Nataliya Trunova, Cesare Gridelli
Background: Longitudinal data on the impact of treatment on quality of life (QoL) in advanced non-small cell lung cancer (NSCLC) are limited. In this palliative setting, treatment that does not deteriorate QoL is key. Here we report longitudinal QoL in patients with squamous NSCLC, receiving ≤4 cycles of nab -paclitaxel/carboplatin combination chemotherapy. Methods: Patients received nab -paclitaxel 100 mg/m2 days 1, 8, 15 + carboplatin area under the curve 6 mg•min/mL day 1 (q3w) for four cycles...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29123433/real-world-practice-patterns-for-patients-with-advanced-non-small-cell-lung-cancer-multicenter-retrospective-cohort-study-in-japan
#12
Hiroshi Isobe, Kiyoshi Mori, Koichi Minato, Hideki Katsura, Kazuko Taniguchi, Ashwini Arunachalam, Smita Kothari, Xiting Cao, Terufumi Kato
Background: Recommended therapies for advanced/metastatic non-small cell lung cancer (NSCLC) have changed with the advent of targeted therapies. The objectives of this retrospective chart review study were to describe treatment patterns, biomarker testing practices, and health care resource use for advanced NSCLC at 5 sites in Japan. Patients and methods: We studied anonymized medical record data of patients aged ≥18 years who initiated systemic therapy for newly diagnosed stage IIIB or IV NSCLC from January 2011 through June 2013...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29089791/comparative-effectiveness-and-safety-of-nab-paclitaxel-plus-carboplatin-vs-gemcitabine-plus-carboplatin-in-first-line-treatment-of-advanced-squamous-cell-non-small-cell-lung-cancer-in-a-us-community-oncology-setting
#13
Raja Mudad, Manish B Patel, Sandra Margunato-Debay, David Garofalo, Lincy S Lal
INTRODUCTION: Real-world comparative effectiveness, safety, and supportive care use of nab -paclitaxel plus carboplatin vs gemcitabine plus platinum were analyzed in patients with advanced or metastatic squamous cell non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients who received ≥ 1 cycle of first-line nab -paclitaxel plus carboplatin or gemcitabine plus platinum were identified from the Navigating Cancer database. Clinical effectiveness endpoints included overall survival (OS) and time to treatment discontinuation (TTD)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29075144/spotlight-on-brigatinib-and-its-potential-in-the-treatment-of-patients-with-metastatic-alk-positive-non-small-cell-lung-cancer-who-are-resistant-or-intolerant-to-crizotinib
#14
REVIEW
Rohit K Jain, Hongbin Chen
In the last decade, there have been major therapeutic advances in the management of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer. Crizotinib was the first approved ALK inhibitor with significant benefits over chemotherapy. However, patients inevitably develop disease progression especially in central nervous system and acquire resistance to crizotinib. Several next-generation ALK inhibitors have been developed to overcome these resistance mechanisms and have demonstrated clinical benefits in crizotinib-refractory non-small cell lung cancer including in central nervous system...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29070957/-egfr-t790m-revealing-the-secrets-of-a-gatekeeper
#15
REVIEW
Brian Ko, Daniel Paucar, Balazs Halmos
Non-small-cell lung cancers that harbor activating mutations in the EGFR gene represent an important molecularly defined subset of lung cancer. Despite dramatic initial responses with first- and second-generation EGFR-directed tyrosine-kinase inhibitors (TKIs) against these cancers, the development of a dominant and frequent resistance mechanism through a threonine-methionine amino acid substitution at position 790 (T790M) of EGFR has limited the long-term efficacy of these targeted therapies. This "gatekeeper" EGFR T790M alteration remains the only validated and relevant second-site resistance mutation for EGFR , allowing for focused research to understand and overcome EGFR T790M-mediated resistance...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/29066938/prognostic-value-of-soluble-major-histocompatibility-complex-class-i-polypeptide-related-sequence-a-in-non-small-cell-lung-cancer-significance-and-development
#16
REVIEW
Roberto Cascone, Annalisa Carlucci, Matteo Pierdiluca, Mario Santini, Alfonso Fiorelli
Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA) is a useful marker in surveillance of lung cancer. High serum sMICA level in patients with non-small-cell lung cancer (NSCLC) seems to be a poor prognostic factor being correlated with poor differentiation and advanced stage. However, the low specificity limits its role as a single prognostic marker of NSCLC, but its evaluation, in addition to standard serum markers, could improve the staging of NSCLC. Despite promising, all current studies are insufficient to assess the real efficiency of sMICA as a prognostic marker of NSCLC, and hence, future studies are required to validate it...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28883747/proton-beam-therapy-in-non-small-cell-lung-cancer-state-of-the-art
#17
REVIEW
Hideyuki Harada, Shigeyuki Murayama
This review summarizes the past and present status of proton beam therapy (PBT) for lung cancer. PBT has a unique characteristic called the Bragg peak that enables a reduction in the dose of normal tissue around the tumor, but is sensitive to the uncertainties of density changes. The heterogeneity in electron density for thoracic lesions, such as those in the lung and mediastinum, and tumor movement according to respiration necessitates respiratory management for PBT to be applied in lung cancer patients. There are two types of PBT - a passively scattered approach and a scanning approach...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28860886/clinical-staging-of-malignant-pleural-mesothelioma-current-perspectives
#18
REVIEW
Maria Bonomi, Costantino De Filippis, Egesta Lopci, Letizia Gianoncelli, Giovanna Rizzardi, Eleonora Cerchiaro, Luigi Bortolotti, Alessandro Zanello, Giovanni Luca Ceresoli
Malignant pleural mesothelioma (MPM) is a disease with limited therapeutic options, the management of which is still controversial. Diagnosis is usually made by thoracoscopy, which allows multiple biopsies with histological subtyping and is indicated for staging purposes in surgical candidates. The recommended and recently updated classification for clinical use is the TNM staging system established by the International Mesothelioma Interest Group and the International Association for the Study of Lung Cancer, which is based mainly on surgical and pathological variables, as well as on cross-sectional imaging...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28860885/osimertinib-in-the-treatment-of-non-small-cell-lung-cancer-design-development-and-place-in-therapy
#19
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Alessandro D'Aveni, Grazia Marabello, Giuseppe Altavilla, Rafael Rosell
The discovery of epidermal growth factor receptor (EGFR) mutations and subsequent demonstration of the efficacy of genotype-directed therapies with EGFR tyrosine kinase inhibitors (TKIs) marked the advent of the era of precision medicine for non-small-cell lung cancer (NSCLC). First- and second-generation EGFR TKIs, including erlotinib, gefitinib and afatinib, have consistently shown superior efficacy and better toxicity compared with first-line platinum-based chemotherapy and currently represent the standard of care for EGFR-mutated advanced NSCLC patients...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28860884/chronic-obstructive-pulmonary-disease-in-patients-with-lung-cancer-prevalence-impact-and-management-challenges
#20
REVIEW
Dionisios Spyratos, Eleni Papadaki, Sofia Lampaki, Theodoros Kontakiotis
Chronic obstructive pulmonary disease (COPD) and lung cancer share a common etiological factor (cigarette smoking) and usually coexist in everyday clinical practice. The prevalence of COPD among newly diagnosed patients with lung cancer sometimes exceeds 50%. COPD is an independent risk factor (2-4 times higher than non-COPD subjects) for lung cancer development. The presence of emphysema in addition to other factors (e.g., smoking history, age) could be incorporated into risk scores in order to define the most appropriate target group for lung cancer screening using low-dose computed tomography...
2017: Lung Cancer: Targets and Therapy
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