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https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#1
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
https://www.readbyqxmd.com/read/28811223/influence-and-mechanism-of-5-aminolevulinic-acid-photodynamic-therapy-on-the-metastasis-of-esophageal-carcinoma
#2
Xiaona Zhang, Longmei Cai, Jingcai He, Xiaoyan Li, Libo Li, Xiaohua Chen, Ping Lan
BACKGROUD: 5-Aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) for the treatment of esophageal cancer was more and more popularly used since it was approved for the treatment of advanced esophageal cancer in 1996. It has been reported to influence the tumor growth and metastasis via a variety of signaling pathways, but its mechanism remains to be further studied. This research studied the effects of ALA-PDT on esophageal carcinoma in vitro and in vivo, discovering its molecular regulating mechanism and the way to enhence the PDT effect...
August 12, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28810546/changes-in-cell-junctions-induced-by-inhibition-of-epidermal-growth-factor-receptor-in-oral-squamous-cell-carcinoma-cells
#3
Yasumasa Kakei, Shun Teraoka, Masaya Akashi, Takumi Hasegawa, Takahide Komori
The benefits of epidermal growth factor receptor (EGFR) targeting in the treatment of head and neck cancer, have been documented. However, a minority of patients with head and neck cancer are unresponsive to EGFR targeting therapies. The present study evaluated the effects and limitations of an EGFR inhibitor on oral squamous cell carcinoma cells, particularly on cell-cell junctions mediated by epithelial (E)-cadherin. HSC-3 oral squamous cell carcinoma cells were treated with the EGFR inhibitor, AG1478 (0, 0...
August 2017: Experimental and Therapeutic Medicine
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
#4
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/28807520/egfr-amplification-plus-gene-expression-profiling-predicts-response-to-combined-radiotherapy-with-egfr-inhibition-a-preclinical-trial-in-10-hnscc-tumour-xenograft-models
#5
Lydia Koi, Steffen Löck, Annett Linge, Cedric Thurow, Sandra Hering, Michael Baumann, Mechthild Krause, Kristin Gurtner
BACKGROUND AND PURPOSE: Improvement of the results of radiotherapy by EGFR inhibitors is modest, suggesting significant intertumoural heterogeneity of response. To identify potential biomarkers, a preclinical trial was performed on ten different human squamous cell carcinoma xenografts of the head and neck (HNSCC) studying in vivo and ex vivo the effect of fractionated irradiation and EGFR inhibition. Local tumour control and tumour growth delay were correlated with potential biomarkers, e...
August 11, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28807234/third-generation-egfr-tkis-in-egfr-mutated-nsclc-where-are-we-now-and-where-are-we-going
#6
REVIEW
A Russo, T Franchina, G R R Ricciardi, V Smiroldo, M Picciotto, M Zanghì, C Rolfo, V Adamo
The therapeutic landscape of Non Small Lung Cancer (NSCLC) has been profoundly changed over the last decade with the clinical introduction of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) and the discovery of EGFR activating mutations as the major predictive factor to these agents. Despite impressive clinical activity against EGFR-mutated NSCLCs, the benefit seen with 1st and 2nd generation EGFR TKIs is usually transient and virtually all patients become resistant. Several different mechanisms of acquired resistance have been reported to date, but the vast majority of patients develop a secondary exon 20 mutation in the ATP-binding site of EGFR, namely T790M...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28806950/precision-medicine-approaches-to-lung-adenocarcinoma-with-concomitant-met-and-her2-amplification
#7
Doo-Yi Oh, Kyungsoo Jung, Ji-Young Song, Seokhwi Kim, Sang Shin, Yong-Jun Kwon, Ensel Oh, Woong-Yang Park, Sang Yong Song, Yoon-La Choi
BACKGROUND: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models. METHODS: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations...
August 10, 2017: BMC Cancer
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
#8
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/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#9
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28801995/inst-ox-05-024-first-line-gemcitabine-oxaliplatin-and-erlotinib-for-primary-hepatocellular-carcinoma-and-bile-duct-cancers-a-multicenter-phase-ii-trial
#10
Yehuda Z Patt, Waheed Murad, Mohammed H Fekrazad, Ari D Baron, Pranshu Bansal, Yanis Boumber, Kim Steinberg, Sang-Joon Lee, Ed Bedrick, Ruofei Du, Fa Chyi Lee
Hepatocellular Carcinoma (HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer (BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor (TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease-control rate (DCR), complete response (CR) + partial response (PR)+ stable disease (SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0...
August 11, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28801616/circulating-cd40-and-scd40l-predict-changes-in-renal-function-in-subjects-with-chronic-kidney-disease
#11
Jeffrey X Xie, Helen Alderson, James Ritchie, Philip A Kalra, Yanmei Xie, Kaili Ren, Hanh Nguyen, Tian Chen, Pamela Brewster, Rajesh Gupta, Lance D Dworkin, Deepak Malhotra, Christopher J Cooper, Jiang Tian, Steven T Haller
Soluble CD40 ligand (sCD40L) has been implicated in the development of renal injury. The CD40 receptor exists in a soluble form, sCD40R, and has been shown to function as a competitive antagonist against CD40 activation. We analyzed whether plasma levels of sCD40L and sCD40R predict changes in renal function in an all-cause chronic kidney disease (CKD) cohort. Stratification of subjects based on sCD40L and sCD40R individually, as well as in combination, demonstrated that sCD40L was directly associated with declines in estimated glomerular filtration rate (eGFR)...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801183/paired-phase-ii-studies-of-erlotinib-bevacizumab-for-advanced-bronchioloalveolar-carcinoma-or-never-smokers-with-advanced-non-small-cell-lung-cancer-swog-s0635-and-s0636-trials
#12
Howard L West, James Moon, Antoinette J Wozniak, Philip Mack, Fred R Hirsch, Martin J Bury, Myron Kwong, Dorothy D Nguyen, Dennis F Moore, Jieling Miao, Mary Redman, Karen Kelly, David R Gandara
BACKGROUND: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636)...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28798270/a-phase-i-dose-escalation-study-of-the-safety-and-pharmacokinetics-of-pictilisib-in-combination-with-erlotinib-in-patients-with-advanced-solid-tumors
#13
Stephen Leong, Rebecca A Moss, Daniel W Bowles, Joseph A Ware, Jing Zhou, Jill M Spoerke, Mark R Lackner, Geetha Shankar, Jennifer L Schutzman, Ruud van der Noll, Emile E Voest, Jan H M Schellens
BACKGROUND: Epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K) are involved in the proliferation and survival of many cancer types. Enhanced antitumor activity may be achieved through combined inhibition of these pathways. We report results for pictilisib (GDC-0941, a class I pan-PI3K inhibitor) plus erlotinib (an EGFR tyrosine kinase inhibitor) in patients with advanced solid tumors. MATERIALS AND METHODS: A 3 + 3 dose-escalation study was carried out at a starting daily dose of 60 mg pictilisib on days 1-21 of a 28-day cycle and 150 mg erlotinib from day 2 of cycle 1...
August 10, 2017: Oncologist
https://www.readbyqxmd.com/read/28798090/egfr-tyrosine-kinase-inhibitors-versus-chemotherapy-in-egfr-wild-type-pre-treated-advanced-nonsmall-cell-lung-cancer-in%C3%A2-daily-practice
#14
Pascale Tomasini, Solenn Brosseau, Julien Mazières, Jean-Philippe Merlio, Michèle Beau-Faller, Jean Mosser, Marie Wislez, L'Houcine Ouafik, Benjamin Besse, Isabelle Rouquette, Didier Debieuvre, Fabienne Escande, Virginie Westeel, Clarisse Audigier-Valette, Pascale Missy, Alexandra Langlais, Frank Morin, Denis Moro-Sibilot, Gérard Zalcman, Fabrice Barlesi
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are approved for second-line treatment of EGFR wild-type (EGFR-wt) nonsmall cell lung cancer (NSCLC). However, results from randomised trials performed to compare EGFR-TKIs with chemotherapy in this population did not show any survival benefit. In the era of immunotherapy, many drugs are approved for second-line treatment of EGFR-wt NSCLC and there is a need to reassess the role of EGFR-TKIs in this setting.The Biomarkers France study is a large nationwide cohort of NSCLC patients tested for EGFR mutations...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28797567/docosahexaenoic-acid-induces-glial-cell-line-derived-neurotrophic-factor-release-in-c6-glioma-cells-implications-of-antidepressant-effects-for-docosahexaenoic-acid
#15
Lanqiu Zhang, Zhuoran Zhu, Zhoubin Tan, Hongyan Luo, Xinwu Hu, Yan Li
Dietary deficiency of n-3 polyunsaturated fatty acids (PUFAs) is involved in the pathophysiology and etiology of major depressive disorder. Supplementation with docosahexaenoic acid (DHA) exerts antidepressant-like effect; however, the molecular mechanism of DHA action remains unclear. Here we examined the effects of DHA on the modulation of glial cell line-derived neurotrophic factor (GDNF), which is essential for neural development, plasticity, neurogenesis, and survival. We demonstrated that DHA treatment significantly increased GDNF release in a concentration dependent manner in rat C6 glioma cells (C6 cells) and primary cultured rat astrocytes, which is also associated with increased expression of GDNF mRNA...
August 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28797448/dual-peptide-mediated-targeted-delivery-of-bioactive-sirnas-to-oral-cancer-cells-in-vivo
#16
Angela A Alexander-Bryant, Haiwen Zhang, Christopher C Attaway, William Pugh, Laurence Eggart, Robert M Sansevere, Lourdes M Andino, Lu Dinh, Liliana P Cantini, Andrew Jakymiw
OBJECTIVES: Despite significant advances in cancer treatment, the prognosis for oral cancer remains poor in comparison to other cancer types, including breast, skin, and prostate. As a result, more effective therapeutic modalities are needed for the treatment of oral cancer. Consequently, in the present study, we examined the feasibility of using a dual peptide carrier approach, combining an epidermal growth factor receptor (EGFR)-targeting peptide with an endosome-disruptive peptide, to mediate targeted delivery of small interfering RNAs (siRNAs) into EGFR-overexpressing oral cancer cells and induce silencing of the targeted oncogene, cancerous inhibitor of protein phosphatase 2A (CIP2A)...
September 2017: Oral Oncology
https://www.readbyqxmd.com/read/28797274/the-pattern-of-kras-mutations-in-metastatic-colorectal-cancer-a-retrospective-audit-from-sri-lanka
#17
Nirmala Dushyanthi Sirisena, Kemal Deen, Dayupathi Eranda Nipunika Mandawala, Pumindu Herath, Vajira Harshadeva Weerabaddana Dissanayake
OBJECTIVE: Activating mutations in the KRAS gene, found in approximately 53% of metastatic colorectal cancer (mCRC) cases, can render epidermal growth factor receptor (EGFR) inhibitors ineffective. Regional differences in these mutations have been reported. This is the first study which aims to describe the pattern of KRAS mutations in a Sri Lankan cohort of mCRC patients. RESULTS: The KRAS genotypes detected in mCRC patients which have been maintained in an anonymized database were retrospectively analyzed...
August 10, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28796259/muc1-induces-acquired-chemoresistance-by-upregulating-abcb1-in-egfr-dependent-manner
#18
Wei Jin, Xiaodong Liao, Yaping Lv, Zhi Pang, Yuming Wang, Quanfu Li, Yahui Liao, Qing Ye, Guoqiang Chen, Kewen Zhao, Lei Huang
Chemoresistance contributes to cancer relapse and increased mortality in a variety of cancer types, raising a pressing need to better understand the underlying mechanism. MUC1 is abnormally overexpressed in numerous carcinomas and associated with poor prognosis. However, the functional significance of MUC1 in chemoresistance has not been fully elucidated. Here, we showed that MUC1 expression was considerably induced in cells that had acquired chemoresistance at both transcriptional and post-translational levels...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#19
REVIEW
Valentina Mazza, Federico Cappuzzo
The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28791656/egfr-as-a-target-for-glioblastoma-treatment-an-unfulfilled-promise
#20
Manfred Westphal, Cecile L Maire, Katrin Lamszus
The receptor for epidermal growth factor (EGFR) is a prime target for cancer therapy across a broad variety of tumor types. As it is a tyrosine kinase, small molecule tyrosine kinase inhibitors (TKIs) targeting signal transduction, as well as monoclonal antibodies against the EGFR, have been investigated as anti-tumor agents. However, despite the long-known enigmatic EGFR gene amplification and protein overexpression in glioblastoma, the most aggressive intrinsic human brain tumor, the potential of EGFR as a target for this tumor type has been unfulfilled...
August 8, 2017: CNS Drugs
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