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Targeted therapy lung cancer

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https://www.readbyqxmd.com/read/28104537/correlation-between-classic-driver-oncogene-mutations-in-egfr-alk-or-ros1-and-22c3-pd-l1-%C3%A2-50-expression-in-lung-adenocarcinoma
#1
Deepa Rangachari, Paul A VanderLaan, Meghan Shea, Xiuning Le, Mark S Huberman, Susumu S Kobayashi, Daniel B Costa
INTRODUCTION: Targeted somatic genomic analysis (EGFR, ALK and ROS1) and PD-L1 tumor proportion score (TPS) by immunohistochemistry (IHC) are used for selection of 1(st)-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported. METHODS: We retrospectively probed the first 71 lung adenocarcinoma-patient pairs from our institution analyzed for PD-L1 IHC using the clone 22C3 pharmDx kit and evaluated co-occurrence of genomic aberrations along with clinical-pathologic characteristics...
January 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28103976/-research-progress-of-targeted-therapy-for-anaplastic-lymphoma-kinase-and-other-rare-driver-genes-in-advanced-non-small-cell-lung-cancer
#2
Quan Zhang, Shucai Zhang
Targeted therapy was one of the major treatments in advanced non-small cell lung cancer (NSCLC) with positive driver genes. This area of research progresses day by day, with novel target discoveries, novel drug development, and use of novel combination treatments. Researchers have also undergone deep investigation about the molecular mechanisms underlying inherent or acquired resistance to these targeted therapies. This review aimed to summarize the advanced developments of targeted therapy for anaplastic lymphoma kinase (ALK) and other rare driver genes in NSCLC...
January 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28103975/-research-progress-of-targeted-therapy-for-egfr-gene-in-non-small-cell-lung-cancer
#3
Hui Zhang, Shucai Zhang
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have brought great clinical benefit to patients with EGFR-sensitive mutations. With the deepening of clinical and basic research, EGFR-TKIs have received more and more attention. In this review, we summarize the latest research development about EGFR-targeted drugs in 2016.
January 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28103970/-a-phase-i-ii-study-of-chemotherapy-concurrent-with-twice-daily-radiotherapy-%C3%A2-schedules-by-intensity-modulated-radiation-therapy-using-simultaneous-integrated-boost-for-limited-stage-small-cell-lung-cancer
#4
Jing You, Huiming Yu, Maxiaowei Song, Chen Shi, Xiaohang Wang, Ye Zheng, Rong Yu, Anhui Shi, Guangying Zhu
BACKGROUND: Twice-daily radiation concurrent with chemotherapy is one of the standard methods for limited-stage small cell lung cancer. The study was to evaluate the feasibility of chemotherapy concurrent with dose-escalating twice-daily radiotherapy by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) approach in patients with limited-stage small cell lung cancer. METHODS: Patients with limited-stage small cell lung cancer were included, treated with twice-daily radiotherapy by SIB-IMRT concurrent with chemotherapy of etoposide plus cisplatin...
January 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28103968/-gene-expression-and-clinical-characteristics-of-molecular-targeted-therapy-%C3%A2-in-non-small-cell-lung-cancer-patients-in-shandong
#5
Xiuli Qiao, Dan Ai, Honglu Liang, Dianbin Mu, Qisen Guo
BACKGROUND: Molecular targeted therapy has gradually become an important treatment for lung cancer, the aim of this research is to analyze the clinicopathologic features associated with the gene mutation status of epidermal growth factor receptor (EGFR), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) and Kirsten rat sarcoma viral oncogene (KRAS) in non-small cell lung cancer (NSCLC) patients and determine the most likely populations to benefit from molecular target therapy treatment...
January 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28103826/tracking-the-origin-of-simultaneous-endometrial-and-ovarian-cancer-by-next-generation-sequencing-a-case-report
#6
Nadejda Valtcheva, Franziska M Lang, Aurelia Noske, Eleftherios P Samartzis, Anna-Maria Schmidt, Elisa Bellini, Daniel Fink, Holger Moch, Markus Rechsteiner, Konstantin J Dedes, Peter J Wild
BACKGROUND: Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations. CASE PRESENTATION: In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary...
January 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28103738/pharmacological-management-of-relapsed-refractory-nsclc-with-chemical-drugs
#7
Niki Karachaliou, Aaron E Sosa, Feliciano Barron Barron, Maria Gonzalez Cao, Mariacarmela Santarpia, Rafael Rosell
Lung cancer is the leading cause of cancer death in both genders. In the early stages the disease is asymptomatic and most patients appear with metastasis at the time of the diagnosis. The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements has changed the treatment landscape and has improved the prognosis of lung cancer patients. Inevitably, all patients initially treated with either chemotherapy or targeted therapies develop resistance and require a second-line therapeutic approach...
January 20, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28102575/bcl-2-family-in-non-small-cell-lung-cancer-its-prognostic-and-therapeutic-implications
#8
Ping-Li Sun, Hironobu Sasano, Hongwen Gao
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Despite significant advances in its research of tumor biology and therapy, the prognosis for this neoplasm has still remained poor. The great majority of anticancer agents, regardless of their mechanisms of action, exert their lethal actions on cancer cells by inducing apoptosis following drug-induced cellular damage. Many reported studies have evaluated the prognostic and therapeutic implications of apoptosis in lung cancer, but their exact clinical value has remained unclear...
January 19, 2017: Pathology International
https://www.readbyqxmd.com/read/28101463/development-of-a-novel-human-single-chain-antibody-against-egfrviii-antigen-by-phage-display-technology
#9
Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Bahman Akbari, Shiva Ahdi Khosroshahi
Purpose: EGFRvIII as the most common mutant variant of the epidermal growth factor receptor is resulting from deletion of exons 2-7 in the coding sequence and junction of exons 1 and 8 through a novel glycine residue. EGFRvIII is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. The aim of the present study was identification of a novel single chain antibody against EGFRvIII as a promising target for cancer therapy. Methods: In this study, a synthetic peptide corresponding to EGFRvIII protein was used for screening a naive human scFv phage library...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28101216/epidermal-growth-factor-receptor-mutation-enhances-expression-of-vascular-endothelial-growth-factor-in-lung-cancer
#10
Ming-Szu Hung, I-Chuan Chen, Paul-Yann Lin, Jr-Hau Lung, Ya-Chin Li, Yu-Ching Lin, Cheng-Ta Yang, Ying-Huang Tsai
Epidermal growth factor receptor (EGFR) activation has been demonstrated to have a critical role in tumor angiogenesis. In the present study, the correlation between EGFR mutations and vascular endothelial growth factor (VEGF) was investigated in lung cancer cell lines and non-small-cell lung cancer (NSCLC) tumor tissues. VEGF levels were significantly increased in culture medium of lung cancer cells and NSCLC tissues with EGFR mutations (H1650 vs. A549, P=0.0399; H1975 vs. A549, P<0.0001). Stable lung cancer cell lines expressing mutant (exon 19 deletion, E746-A750; exon 21 missense mutation, L858R) and wild-type EGFR genes were established...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28099915/liquid-biopsy-genotyping-in-lung-cancer-ready-for-clinical-utility
#11
Wei-Lun Huang, Yi-Lin Chen, Szu-Chun Yang, Chung-Liang Ho, Fang Wei, David T Wong, Wu-Chou Su, Chien-Chung Lin
Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care...
January 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099841/targeted-inhibition-of-egfr-and-glutaminase-induces-metabolic-crisis-in-egfr-mutant-lung-cancer
#12
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Clara Magyar, Daniel Braas, Thomas Graeber, Nicholas J Jackson, Johannes Czernin, Ethan Emberley, Matthew Gross, Julie Janes, Andy Mackinnon, Alison Pan, Mirna Rodriguez, Melissa Works, Winter Zhang, Francesco Parlati, Susan Demo, Edward Garon, Kostyantyn Krysan, Tonya C Walser, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28099079/lymphangioleiomyomatosis-a-monogenic-model-of-malignancy
#13
Vera P Krymskaya, Francis X McCormack
Lymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All pulmonary structures become infiltrated with benign-appearing spindle and epithelioid cells (LAM cells) that express smooth-muscle and melanocyte-lineage markers, harbor mTOR-activating mutations in tuberous sclerosis complex (TSC) genes, and recruit abundant stromal cells. Elaboration of lymphangiogenic growth factors and matrix remodeling enzymes by LAM cells enables their access to lymphatic channels and likely drives the cystic lung remodeling that often culminates in respiratory failure...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/28096714/evolving-cancer-classification-in-the-era-of-personalized-medicine-a-primer-for-radiologists
#14
REVIEW
Ailbhe C O'Neill, Jyothi P Jagannathan, Nikhil H Ramaiya
Traditionally tumors were classified based on anatomic location but now specific genetic mutations in cancers are leading to treatment of tumors with molecular targeted therapies. This has led to a paradigm shift in the classification and treatment of cancer. Tumors treated with molecular targeted therapies often show morphological changes rather than change in size and are associated with class specific and drug specific toxicities, different from those encountered with conventional chemotherapeutic agents...
January 2017: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/28095746/targeting-of-herbal-bioactives-through-folate-receptors-a-novel-concept-to-enhance-intracellular-drug-delivery-in-cancer-therapy
#15
Anshita Gupta, Chanchal Deep Kaur, Shailendra Saraf, Swarnlata Saraf
Targeted drug delivery through folate receptor (FR) has emerged as a most biocompatible, target oriented, and non-immunogenic cargoes for the delivery of anticancer drugs. FRs are highly overexpressed in many tumor cells (like ovarian, lung, breast, kidney, brain, endometrial, and colon cancer), and targeting them through conjugates bearing specific ligand with encapsulated nanodrug moiety is undoubtedly, a promising approach toward tumor targeting. Folate, being an endogenous ligand, can be exploited well to affect various cellular events occurring during the progress of tumor, in a more natural and definite way...
January 17, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28094211/likelihood-of-unacceptable-normal-tissue-doses-in-breast-cancer-patients-undergoing-regional-nodal-irradiation-in-routine-clinical-practice
#16
Jose Bazan, Dominic DiCostanzo, Karla Kuhn, Lonika Majithia, Allison Quick, Nilendu Gupta, Julia White
PURPOSE: As indications for regional nodal irradiation (RNI) for breast cancer have expanded, so too has scrutiny over potential late toxicity from radiotherapy. This emphasizes the need for careful radiation treatment planning to maximize the therapeutic ratio. We sought to evaluate how often unacceptable doses (UDs) to organs at risk (OARs) occur and the associated factors for patients receiving RNI in daily practice. METHODS AND MATERIALS: Treatment records of patients who received RNI from February 2012 to May 2015 were studied...
October 19, 2016: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28093296/inhibition-of-cd44v3-and-cd44v6-function-blocks-tumor-invasion-and-metastatic-colonization
#17
Michal Zaiden, Valeria Feinshtein, Ayelet David
The prevention of cancer cell dissemination and secondary tumor formation are major goals of cancer therapy. Here, we report on the development of a new CD44-targeted copolymer carrying multiple copies of the A5G27 peptide, known for its ability to bind specifically to CD44v3 and CD44v6 on cancer cells and inhibit tumor cell migration, invasion, and angiogenesis. We hypothesized that conjugation of A5G27 to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer would enhance tumor tissue accumulation, promote selective binding to cancer cells, with concomitant increased inhibition of cancer cell invasiveness and migration...
January 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28093244/novel-mutations-on-egfr-leu792-potentially-correlate-to-acquired-resistance-to-osimertinib-in-advanced-nsclc
#18
Kai Chen, Fei Zhou, Wenxiang Shen, Tao Jiang, Xue Wu, Xiaoling Tong, Yang W Shao, Songbing Qin, Caicun Zhou
Osimertinib is an irreversible third generation EGFR tyrosine kinase inhibitor (TKI) and has shown outstanding performances in treating EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) patients, but acquired resistance is inevitable. EGFR C797S is the most notable resistance mechanism to this drug, but other EGFR mutations may also exist. In three lung adenocarcinoma patients resistant to osimertinib, we identified recurrent novel mutations at EGFR Leu792 codon by targeted next generation sequencing (NGS) of cell free DNA (cfDNA) from plasma or pleural effusion...
January 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28089762/long-terms-results-of-a-trial-of-concurrent-chemotherapy-and-escalating-doses-of-radiation-for-unresectable-non-small-cell-lung-cancer-ncctg-n0028-alliance
#19
Steven E Schild, Shauna L Hillman, Angelina D Tan, Helen J Ross, William L McGinnis, Yolanda A Garces, David L Graham, Alex A Adjei, James R Jett
INTRODUCTION OR HYPOTHESIS: This phase I/II trial was originally designed to determine the maximally tolerated dose(MTD) of thoracic radiotherapy(TRT) as part of a combined modality approach. This report includes the long-term outcome of patients treated on this study. The phase II portion was never completed as RTOG-0617 opened before it was concluded. METHODS: The MTD was defined as 74Gy in 37 fractions in this study. Twenty-five patients with unresectable non-small cell lung cancer(NSCLC) were treated with 2Gy daily fractions and concurrent weekly carboplatin and paclitaxel...
January 12, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28089420/regression-of-intracranial-meningioma-following-treatment-with-nivolumab-case-report-and-review-of-the-literature
#20
Efrat Gelerstein, Assaf Berger, Tali Jonas-Kimchi, Ido Strauss, Andrew A Kanner, Deborah T Blumenthal, Maya Gottfried, Nevo Margalit, Zvi Ram, Tal Shahar
The treatment of refractory meningiomas remains a challenge for both neurosurgeons and neuro-oncologists. There have been no clinical reports of the use or effects of anti-PD-1 therapy in patients with meningioma. We describe a patient whose intracranial meningioma decreased significantly in size after treatment with nivolumab, a monoclonal antibody targeting PD-1, for a concomitant advanced lung cancer. This is the first clinical report suggesting that antibodies targeting PD-1 are effective in treating meningioma...
January 12, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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