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https://www.readbyqxmd.com/read/29355391/updated-molecular-testing-guideline-for-the-selection-of-lung-cancer-patients-for-treatment-with-targeted-tyrosine-kinase-inhibitors-guideline-from-the-college-of-american-pathologists-the-international-association-for-the-study-of-lung-cancer-and-the-association
#1
Neal I Lindeman, Philip T Cagle, Dara L Aisner, Maria E Arcila, Mary Beth Beasley, Eric Bernicker, Carol Colasacco, Sanja Dacic, Fred R Hirsch, Keith Kerr, David J Kwiatkowski, Marc Ladanyi, Jan A Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benjamin Solomon, Lesley H Souter, Erik Thunnissen, Ming S Tsao, Christina B Ventura, Murry W Wynes, Yasushi Yatabe
CONTEXT: - In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: - To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update...
January 22, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29352732/long-term-effects-of-crizotinib-in-alk-positive-tumors-excluding-nsclc-a-phase-1b-open-label-study
#2
Carlo Gambacorti-Passerini, Sergey Orlov, Li Zhang, Fadi Braiteh, Huiqiang Huang, Taito Esaki, Keizo Horibe, Jin-Seok Ahn, Joseph T Beck, William Jeffrey Edenfield, Yuankai Shi, Matthew Taylor, Kenji Tamura, Brian A Van Tine, Shang-Ju Wu, Jolanda Paolini, Paulina Selaru, Tae Min Kim
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK-positive or ROS1-positive advanced non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large-cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single-arm, open-label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK-positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily...
January 20, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29344953/established-emerging-and-elusive-molecular-targets-in-the-treatment-of-lung-cancer
#3
REVIEW
Jean-Nicolas Gallant, Christine M Lovly
Although histological subtype still underlies tumor classification and treatment, the recognition that lung cancer is, largely, a genetic disease has prompted a push to reconfigure cancer taxonomies according to molecular criteria. In this review, we discuss established (e.g. EGFR, ALK, ROS1, PD-1/PD-L1), emerging (e.g. MET, RET, NTRK), and elusive (e.g. TP53, KRAS, MYC) molecular targets in the treatment of lung cancer. We synthesize a large and rapidly growing body of literature regarding the discovery and therapeutic inhibition of these targets in lung cancer...
January 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29343973/a-patient-with-classic-biphasic-pulmonary-blastoma-harboring-cd74-ros1-fusion-responds-to-crizotinib
#4
Zhaoting Meng, Peng Chen, Fenglin Zang, Ying Liu, Xiaoyan Xu, Yudong Su, Jinliang Chen, Li Lin, Lu Zhang, Tengfei Zhang
Pulmonary blastoma (PB) is a rare aggressive lung malignancy with a poor prognosis. Surgical resection is the treatment of choice for localized disease, and there are no standard treatment guidelines for metastatic PB. Due to its rareness, its molecular profile has not been elucidated. We present the first case of classic biphasic pulmonary blastoma (CBPB) with CD74-ROS1 rearrangement in a 44-year-old Asian female with stage IV disease diagnosed using capture-based ultra-deep targeted sequencing. It has been reported that ROS1 rearranged lung adenocarcinoma and squamous cell carcinoma are sensitive to crizotinib, an ALK/MET/ ROS1 multitargeted tyrosine kinase inhibitor...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29325035/amplicon-based-next-generation-sequencing-of-plasma-cell-free-dna-for-detection-of-driver-and-resistance-mutations-in-advanced-non-small-cell-lung-cancer
#5
N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1 and other rare genotypes) were collected while on therapy and analyzed, blinded to tumor genotype...
January 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29295663/ros1-rearrangement-in-a-case-of-classic-biphasic-pulmonary-blastoma
#6
Taylor M Jenkins, Jennifer J D Morrissette, John C Kucharczuk, Charuhas G Deshpande
Classic biphasic pulmonary blastoma (CBPB) is a rare and aggressive type of non-small cell lung carcinoma (NSCLC) presenting in adults in the fourth to fifth decade. The prognosis is poor and after surgical resection, therapeutic options are often limited. ROS1 is a proto-oncogene receptor tyrosine kinase that has been identified in some types of NSCLC. We report a case of a 36-year-old woman with CBPB, which was subsequently found to have a ROS1 rearrangement. This is the first reported case of a ROS1-rearranged CBPB...
December 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29290262/gcc2-alk-as-a-targetable-fusion-in-lung-adenocarcinoma-and-its-enduring-clinical-responses-to-alk-inhibitors
#7
Junhong Jiang, Xue Wu, Xiaoling Tong, Wangzhi Wei, Anan Chen, Xiaonan Wang, Yang W Shao, Jianan Huang
OBJECTIVES: ALK, RET and ROS1 fusions have been identified as treatable targets in 5%-15% of non-small-cell lung cancers, and thanks to the advanced sequencing technologies, their new partner genes have been steadily detected. Here we identified a rare fusion of ALK (GCC2-ALK) in a patient with advanced lung adenocarcinoma and monitored the treatment efficacy of ALK inhibitors on this patient. We further performed in vitro functional studies of this fusion protein for evaluating its oncogenic potential...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29277178/-clinical-significance-and-mechanism-of-pi3k-p110%C3%AE-overexpression%C3%A2-in-non-small-cell-lung-cancer
#8
Yan Xiong, Linlin Qu, Dong Li, Ying Wang, Ting Li
BACKGROUND: Phosphatidylinositide 3-kinases (PI3K) pathway is one of the most important pathway in cells, which plays an important role in proliferation, growth, differentiation and mobility of cells. The aberrant activation of PI3K pathway was exsited in 50%-70% cases of non-small cell lung cancer (NSCLC). As the key point in PI3K pathway, expression of PI3K plays a critical role in activity of the pathway, which is closely related with the initiation and development of NSCLC, furthermore with the response of tumor to target treatment...
December 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29261000/successful-treatment-using-apatinib-with-or-without-docetaxel-in-heavily-pretreated-advanced-non-squamous-non-small-cell-lung-cancer-a-case-report-and-literature-review
#9
Fengying Wu, Shijia Zhang, Guanghui Gao, Jing Zhao, Shengxiang Ren, Caicun Zhou
Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. A phase II clinical trial demonstrated the survival benefit of apatinib monotherapy in advanced NSCLC...
December 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29251824/dual-drive-coexistence-of-eml4-alk-and-tpm3-ros1-fusion-in-advanced-lung-adenocarcinoma
#10
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Jian-Guo Wei, Kai-Qi Du
We report a case of concomitant EML4-ALK and TPM3-ROS1 fusion in non-small cell lung cancer (NSCLC) in a 47-year-old Chinese man and review the clinical characteristics of this type double of fusion. The patient presented with a local tumor of the left upper lobe and underwent thoracoscopy. Postoperative surgical pathologic staging revealed T1a N0 M0 stage IA. Histological examination of the tumor showed lung adenocarcinoma. Ventana ALK (D5F3) assay of the left lung tissue was ALK negative; however, immunohistochemical assay was positive for ROS1 protein...
December 18, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29251734/ligation-dependent-rt-pcr-a-new-specific-and-low-cost-technique-to-detect-alk-ros-and-ret-rearrangements-in-lung-adenocarcinoma
#11
Nicolas Piton, Philippe Ruminy, Claire Gravet, Vinciane Marchand, Élodie Colasse, Aude Lamy, Cécile Le Naoures Mear, Fréderic Bibeau, Florent Marguet, Florian Guisier, Mathieu Salaün, Luc Thiberville, Fabrice Jardin, Jean-Christophe Sabourin
Detection of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), and rearranged during transfection (RET) gene rearrangements in lung adenocarcinoma is usually performed by immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH), which is an expensive and difficult technique. Ligation-dependent reverse transcription polymerase chain reaction (RT-PCR) multiplex technique can detect gene rearrangements using probes specifically hybridized to either side of the break point...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29251665/molecular-pathology-of-lung-cancer-current-status-and-perspectives
#12
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/29237803/anti-tumor-activity-of-entrectinib-a-pan-trk-ros1-and-alk-inhibitor-in-etv6-ntrk3-positive-acute-myeloid-leukemia
#13
Kristen M Smith, Patrick C Fagan, Elena Pomari, Giuseppe Germano, Chiara Frasson, Colin Walsh, Ian M Silverman, Paolo Bonvini, Gang Li
Activation of tropomyosin receptor kinase (TRK) family tyrosine kinases by chromosomal rearrangement has been shown to drive a wide range of solid tumors and hematologic malignancies. TRK fusions are actionable targets as evidenced by recent clinical trial results in solid tumors. Entrectinib (RXDX-101) is an investigational, orally available, CNS-active, highly potent and selective kinase inhibitor against TRKA/B/C, ROS1 and ALK kinase activities. Here, we demonstrate that TRK kinase inhibition by entrectinib selectively targets preclinical models of TRK fusion-driven hematologic malignancies...
December 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29230123/molecular-targets-in-non-small-cell-lung-cancer
#14
REVIEW
Ryan Griffin, Robert A Ramirez
Background: Lung cancer is the second most common cancer in the United States among men and women, and it is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases. Historically, patients with metastatic NSCLC received similar cytotoxic chemotherapy regimens. Genotyping studies have revealed genetic/molecular abnormalities in lung cancer. These driver mutations render a cancer dependent on that specific mutation's biochemical pathway for its growth and survival...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29227119/-molecular-pathology-of-lung-cancer-in-routine-diagnostic-practice-2017-update
#15
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/29219616/next-generation-sequencing-approach-to-non-small-cell-lung-carcinoma-yields-more-actionable-alterations
#16
Mitra Mehrad, Somak Roy, Humberto Trejo Bittar, Sanja Dacic
CONTEXT: - Different testing algorithms and platforms for EGFR mutations and ALK rearrangements in advanced-stage lung adenocarcinoma exist. The multistep approach with single-gene assays has been challenged by more efficient next-generation sequencing (NGS) of a large number of gene alterations. The main criticism of the NGS approach is the detection of genomic alterations of uncertain significance. OBJECTIVE: - To determine the best testing algorithm for patients with lung cancer in our clinical practice...
December 8, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29217530/the-impact-of-smoking-and-tp53-mutations-in-lung-adenocarcinoma-patients-with-targetable-mutations-the-lung-cancer-mutation-consortium-lcmc2
#17
Dara L Aisner, Lynette M Sholl, Lynne Berry, Michael Rossi, Heidi Chen, Junya Fujimoto, Andre L Moreira, Suresh Ramalingam, Liza C Villaruz, Gregory A Otterson, Eric B Haura, Katerina Politi, Bonnie S Glisson, Jeremy Cetnar, Edward Garon, Joan Schiller, Saiama Waqar, Lecia V Sequist, Julie R Brahmer, Yu Shyr, Kelly Kugler, Ignacio Ivan Wistuba, Bruce E Johnson, John D Minna, Mark G Kris, Paul A Bunn, David J Kwiatkowski
PURPOSE Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. PATIENTS AND METHODS Sixteen U.S. institutions enrolled 1367 lung cancer patients in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and immunohistochemistry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29198084/-the-impact-of-molecular-profiling-using-next-generation-sequencing-in-advanced-lung-cancer
#18
Anna Belilovski Rozenblum, Maya Ilouze, Elizabeth Dudnik, Lior Soussan-Gutman, Addie Dvir, Nir Peled
BACKGROUND: In the last decade, important advances in understanding the lung cancer cellular signal pathways have led to the designing of targeted drugs that significantly prolong survival. Recent data shows that 64% of lung adenocarcinomas harbor at least one activating driver mutation, including treatable mutations such as RET, ERBB2 (HER-2) and ROS1 gene mutations, besides the regularly screened ALK and EGFR genes. Next-Generation Sequencing (NGS) reveals more clinically meaningful genomic alterations as compared to currently used diagnostic tests...
November 2017: Harefuah
https://www.readbyqxmd.com/read/29187012/targeted-therapies-in-non-small-cell-lung-cancer-a-focus-on-alk-ros1-tyrosine-kinase-inhibitors
#19
Assunta Sgambato, Francesca Casaluce, Paolo Maione, Cesare Gridelli
Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define important molecular subgroups of advanced non-small cell lung cancer (NSCLC). The identification of these genetic driver alterations created new potential for highly active therapeutic interventions. After discovery of ALK rearrangements in NSCLC, it was recognized that these confer sensitivity to ALK inhibition. Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC...
January 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29174814/design-synthesis-biological-evaluation-and-molecular-modeling-of-novel-2-amino-4-1-phenylethoxy-pyridine-derivatives-as-potential-ros1-inhibitors
#20
Yuanxin Tian, Tingting Zhang, Lifan Long, Zhonghuang Li, Shanhe Wan, Guangfa Wang, Yonghuan Yu, Ju Hou, Xiaoyun Wu, Jiajie Zhang
With the aim of discovering potential and selective inhibitors targeting ROS1 kinase, we rationally designed, synthesized and evaluated two series of novel 2-amino-pyridine derivatives with 1-phenylethoxy at C-3 and C-4 position. The enzymic assays results indicated that six of the new compounds 13b-13d and 14a-14c showed remarkably higher inhibitory activities against ROS1 kinase. The most promising compounds, 13d and 14c displayed the most desired ROS1 inhibitory activity with IC50 values of 440 nM and 370 nM respectively...
November 3, 2017: European Journal of Medicinal Chemistry
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