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Crizotinib

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https://www.readbyqxmd.com/read/28209203/crizotinib-associated-renal-cysts-carcs-incidence-and-patterns-of-evolution
#1
Laird B Cameron, Damian H S Jiang, Kate Moodie, Catherine Mitchell, Benjamin Solomon, Bimal Kumar Parameswaran
BACKGROUND: Novel therapeutic agents recently introduced for the treatment of cancer have several unusual side effects. An increased incidence of renal cystic lesions, often with features concerning for malignancy or infection, has been reported in patients with anaplastic lymphoma kinase (ALK) - rearranged advanced non-small cell lung cancer (NSCLC) treated with Crizotinib. Many of these lesions undergo spontaneous resolution despite developing complex features on imaging. We assess the incidence and patterns of evolution of Crizotinib Associated Renal Cysts [CARCs] at our institute and provide histopathology correlation of their benign nature...
February 16, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/28195686/diagnosis-of-anaplastic-lymphoma-kinase-rearrangement-in-cytological-samples-through-a-fluorescence-in-situ-hybridization-based-assay-cytological-smears-versus-cell-blocks
#2
Federica Zito Marino, Giulio Rossi, Matteo Brunelli, Maria Gabriella Malzone, Giuseppina Liguori, Giuseppe Bogina, Alessandro Morabito, Gaetano Rocco, Renato Franco, Gerardo Botti
Anaplastic lymphoma kinase (ALK) status analysis of lung cytological specimens should be successfully encouraged in routine practice because biopsy specimens are not always available. To date, the US Food and Drug Administration has approved both fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) as diagnostic tests for identifying ALK-positive patients eligible for treatment with crizotinib. Although ALK IHC is an optimal diagnostic tool, FISH becomes mandatory in equivocal cases. ALK FISH of paraffin-embedded tissue material is still the gold standard, whereas the cytological specimen assay has not yet been completely standardized...
February 14, 2017: Cancer
https://www.readbyqxmd.com/read/28183714/dichotomous-alk-ihc-is-a-better-predictor-for-alk-inhibition-outcome-than-traditional-alk-fish-in-advanced-non-small-cell-lung-cancer
#3
Anthonie van der Wekken, Rianne Pelgrim, Nils 't Hart, Naomi Werner, Mirjam Mastik, Lizza Hendriks, Erik Hfm van der Heijden, Monika Looijen-Salamon, A Joop de Langen, Jeske Staal-van den Brekel, Sietske Riemersma, Ben E van den Borne, Ernst-Jan M Speel, Anne-Marie C Dingemans, T Jeroen N Hiltermann, Anke van den Berg, Wim Timens, Ed Schuuring, Harry Jm Groen
ALK rearrangement detection using fluorescence in situ hybridization (FISH) is the standard test to identify non-small cell lung carcinoma (NSCLC) patients eligible for treatment with ALK inhibitors. Recently ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of advanced NSCLC patients with ALK activation using both dichotomous immunohistochemical staining (IHC) and FISH. Design Stage IV NSCLC patients treated with crizotinib were selected...
February 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28178969/neuroblastoma-treatment-in-the-post-genomic-era
#4
REVIEW
Maria Rosaria Esposito, Sanja Aveic, Anke Seydel, Gian Paolo Tonini
Neuroblastoma is an embryonic malignancy of early childhood originating from neural crest cells and showing heterogeneous biological, morphological, genetic and clinical characteristics. The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patients.High-throughput technologies in the Omics disciplines are leading to significant insights into the molecular pathogenesis of neuroblastoma. Nonetheless, further study of Omics data is necessary to better characterise neuroblastoma tumour biology...
February 8, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28174489/alk-gene-expression-status-in-pleural-effusion-predicts-tumor-responsiveness-to-crizotinib-in-chinese-patients-with-lung-adenocarcinoma
#5
Zheng Wang, Xiaonan Wu, Xiaohong Han, Gang Cheng, Xinlin Mu, Yuhui Zhang, Di Cui, Chang Liu, Dongge Liu, Yuankai Shi
OBJECTIVE: The relationship between anaplastic lymphoma kinase (ALK) expression in malignant pleural effusion (MPE) samples detected only by Ventana immunohistochemistry (IHC) ALK (D5F3) and the efficacy of ALK-tyrosine kinase inhibitor therapy is uncertain. METHODS: Ventana anti-ALK (D5F3) rabbit monoclonal primary antibody testing was performed on 313 cell blocks of MPE samples from Chinese patients with advanced lung adenocarcinoma, and fluorescence in situ hybridization (FISH) was used to verify the ALK gene status in Ventana IHC ALK (D5F3)-positive samples...
December 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28167572/an-oncogenic-alk-fusion-and-an-rras-mutation-in-kras-mutation-negative-pancreatic-ductal-adenocarcinoma
#6
Yoko Shimada, Takashi Kohno, Hideki Ueno, Yoshinori Ino, Hideyuki Hayashi, Takashi Nakaoku, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Kazuaki Shimada, Takuji Okusaka, Nobuyoshi Hiraoka
PURPOSE: Oncogenic mutations in the KRAS gene are a well-known driver event, occurring in >95% of pancreatic cancers. The objective of this study was to identify driver oncogene aberrations in pancreatic cancers without the KRAS mutation. METHODS: Whole-exome and transcriptome sequencing was performed on four cases of KRAS mutation-negative pancreatic ductal adenocarcinoma, which were identified in a cohort of 100 cases. RESULTS: One case harbored an oncogenic DCTN1-ALK fusion...
February 6, 2017: Oncologist
https://www.readbyqxmd.com/read/28156657/toxicities-of-the-anti-pd-1-immune-checkpoint-antibody-nivolumab-in-the-acute-inpatient-setting
#7
(no author information available yet)
: 227 Background: Knowledge of immune-system regulation led to the discovery of immune checkpoints molecules, which have demonstrated anti-tumor activity across various malignancies. These advances represent a new set of challenges for clinicians, including non-oncologists treating the cancer patient, who must develop a working knowledge of the mode of action of these agents, their unique response kinetics, and how to diagnose and effectively manage their toxicities. Nivolumab is a monoclonal immune checkpoint antibody that binds to the PD-1 receptor on T-cells, blocking PD-1 pathway-mediated anti-tumor immune response inhibition...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28156651/oams-at-the-end-the-end-of-the-beginning-or-the-beginning-of-the-end
#8
Barbara Marie Galligan, Chintan Shah, Iris Chen Zhao, Brian Paciotti, Nathan Fairman, Quy Tran
: 229 Background: In 2001, after three months of review, the FDA approved the oral anticancer agent imatinib, making it the fastest approval in FDA history. Since then, the FDA has approved over 40 oral anti-cancer medications (OAMs) and the number continues to rise, transforming cancer care, improving survival in specific cancers and providing new hope. However, the rapid development of OAMs has produced uncertainty over the best use of these new medications, particularly at the end of life...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28152720/comparison-of-real-world-acute-care-interventions-aci-in-patients-pts-with-advanced-non-small-cell-lung-cancer-adv-nsclc-treated-with-chemotherapy-versus-targeted-therapies
#9
Beata Korytowsky, Menaka Bhor, Ken Tuell, Bruce A Feinberg
: 37 Background: This analysis compared the frequency of ACI for any cause (emergency room [ER] visits, hospitalizations, and readmissions) to better understand the burden of treatment in adv NSCLC pts treated with chemotherapy (chemo) vs targeted therapy (TT). METHODS: Using Inovalon's MORE(2) Registry claims data, adv NSCLC pts treated with antineoplastics identified by ICD-9 codes from July 2013-2014 were selected. Inclusion: pts >18 y who received first-line (1L) systemic therapy within 6 mo of diagnosis...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28149753/achievements-and-future-developments-of-alk-tkis-in-the-management-of-cns-metastases-from-alk-positive-nsclc
#10
REVIEW
Lorenza Landi, Federico Cappuzzo
Non-small cell lung cancer (NSCLC) represents the paradigm of personalized treatment of human cancer. Several oncogenic druggable alterations have been so far identified, with anaplastic lymphoma kinase (ALK) gene rearrangements being one of the newest and most appealing. Presence of ALK fusions is associated with some particular clinical and pathological features, including a preferential seeding into the central nervous system (CNS). In addition, ALK rearrangements are recognized as the strongest predictor for benefit of anti-ALK therapy...
December 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28147239/a-sensitive-alk-immunohistochemistry-companion-diagnostic-test-identifies-patients-eligible-for-treatment-with-crizotinib
#11
Trish Thorne-Nuzzo, Crystal Williams, Alice Catallini, June Clements, Shalini Singh, James Amberson, Kim Dickinson, Zoran Gatalica, Steffan N Ho, Isabell Loftin, Abigail McElhinny, Penny Towne
INTRODUCTION: The availability of high quality, rigorously validated diagnostic tests that can be broadly implemented is necessary to efficiently identify patients with anaplastic lymphoma kinase (ALK) NSCLC who can potentially benefit from treatment with crizotinib. Here we present data on the recently approved VENTANA ALK (D5F3) CDx Assay (ALK (D5F3) CDx), the only immunohistochemistry (IHC) based assay linked to treatment outcome. METHODS: NSCLC specimens prospectively tested for ALK status by Flourescent In-situ Hybridization (FISH) in the PROFILE 1014 clinical trial of crizotinib versus chemotherapy (N=1018, including 179 ALK(+) and 754 ALK(-) specimens), were evaluated using the ALK (D5F3) CDx assay...
January 29, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28146421/the-hdac-inhibitor-ar42-interacts-with-pazopanib-to-kill-trametinib-dabrafenib-resistant-melanoma-cells-in-vitro-and-in-vivo
#12
Laurence Booth, Jane L Roberts, Cindy Sander, John Lee, John M Kirkwood, Andrew Poklepovic, Paul Dent
Studies focused on the killing of activated B-RAF melanoma cells by the histone deacetylase (HDAC) inhibitor AR42. Compared to other tumor cell lines, PDX melanoma isolates were significantly more sensitive to AR42-induced killing. AR42 and the multi-kinase inhibitor pazopanib interacted to activate: an eIF2α-Beclin1 pathway causing autophagosome formation; an eIF2α-DR4/DR5/CD95 pathway; and an eIF2α-dependent reduction in the expression of c-FLIP-s, MCL-1 and BCL-XL. AR42 did not alter basal chaperone activity but increased the ability of pazopanib to inhibit HSP90, HSP70 and GRP78...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28138027/met-copy-number-gain-is-associated-with-gefitinib-resistance-in-leptomeningeal-carcinomatosis-of-egfr-mutant-lung-cancer
#13
Shigeki Nanjo, Sachiko Arai, Wei Wang, Shinji Takeuchi, Tadaaki Yamada, Akito Hata, Nobuyuki Katakami, Yasunori Okada, Seiji Yano
Leptomeningeal carcinomatosis (LMC) occurs frequently in EGFR-mutant lung cancer, and develops acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This study aimed to clarify the mechanism of EGFR-TKI resistance in LMC and seek for a novel therapeutic strategy. We examined EGFR mutations, including the T790M gatekeeper mutation, in 32 re-biopsy specimens from 12 LMC and 20 extracranial lesions of EGFR-mutant lung cancer patients who became refractory to EGFR-TKI treatment. All the 32 specimens had the same baseline EGFR mutations, but the T790M mutation was less frequent in LMC specimens than in extracranial specimens (8% vs...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#14
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28081478/pulmonary-sarcomatoid-carcinoma-with-alk-rearrangement-frequency-clinical-pathologic-characteristics-and-response-to-alk-inhibitor
#15
Xinru Chen, Yu Zhang, Jiabin Lu, Chunwei Xu, Jianzhong Liang, Fang Wang, Wenyong Sun, Sangao Fang, Jingping Yuan, Huijuan Wang, Hui Wang, Xuewen Liu, Likun Chen
PURPOSE: The incidence of anaplastic lymphoma kinase (ALK) rearrangement in pulmonary sarcomatoid carcinoma (PSC) is controversial. In this study, we aimed to reveal the reliable frequency and the clinical-pathologic characteristics of pulmonary sarcomatoid carcinoma (PSC) with ALK rearrangement in Chinese population, and to provide insight into the translatability of anti-ALK treatment in this treatment-refractory disease. METHODS: Immunohistochemistry (IHC) using a Ventana anti-ALK (D5F3) rabbit monoclonal antibody was performed in 141 PSC specimens collected from multiple medical centers...
January 9, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28077299/anaplastic-lymphoma-kinase-alk-inhibitors-in-the-treatment-of-alk-driven-lung-cancers
#16
REVIEW
Robert Roskoski
Anaplastic lymphoma kinase is expressed in two-thirds of the anaplastic large-cell lymphomas as an NPM-ALK fusion protein. Physiological ALK is a receptor protein-tyrosine kinase within the insulin receptor superfamily of proteins that participates in nervous system development. The EML4-ALK fusion protein and four other ALK-fusion proteins play a fundamental role in the development in about 5% of non-small cell lung cancers. The amino-terminal portions of the ALK fusion proteins result in dimerization and subsequent activation of the ALK protein kinase domain that plays a key role in the pathogenesis of various tumors...
January 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28075018/c-met-as-a-potential-target-for-the-treatment-of-gastrointestinal-cancer-current-status-and-future-perspectives
#17
REVIEW
Afsaneh Bahrami, Soodabeh Shahidsales, Majid Khazaei, Majid Ghayour-Mobarhan, Mina Maftouh, Seyed Mahdi Hassanian, Amir Avan
Aberrant activation of the HGF/c-Met signalling pathways is shown to be related with cell proliferation, progression, metastasis and worse prognosis in several tumor types, including gastrointestinal cancers, suggesting its value as a stimulating-target for cancer-therapy. Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement. The main aim of current review is to give an overview on the role of c-Met/HGF pathway in gastrointestinal cancer, in preclinical and clinical trials...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28066567/sequencing-alk-inhibitors-alectinib-in-crizotinib-resistant-patients-a-phase-2-trial-by-shaw-et-al
#18
EDITORIAL
Laura Mezquita, Benjamin Besse
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28065466/sequential-use-of-anaplastic-lymphoma-kinase-inhibitors-in-japanese-patients-with-alk-rearranged-non-small-cell-lung-cancer-a%C3%A2-retrospective-analysis
#19
Tetsuhiko Asao, Yutaka Fujiwara, Kota Itahashi, Shinsuke Kitahara, Yasushi Goto, Hidehito Horinouchi, Shintaro Kanda, Hiroshi Nokihara, Noboru Yamamoto, Kazuhisa Takahashi, Yuichiro Ohe
BACKGROUND: Second-generation anaplastic lymphoma kinase (ALK) inhibitors, such as alectinib and ceritinib, have recently been approved for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). An optimal strategy for using 2 or more ALK inhibitors has not been established. We sought to investigate the clinical impact of sequential use of ALK inhibitors on these tumors in clinical practice. PATIENTS AND METHODS: Patients with ALK-rearranged NSCLC treated from May 2010 to January 2016 at the National Cancer Center Hospital were identified, and their outcomes were evaluated retrospectively...
December 7, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28056412/toxicity-of-concurrent-stereotactic-radiotherapy-and-targeted-therapy-or-immunotherapy-a-systematic-review
#20
REVIEW
Stephanie G C Kroeze, Corinna Fritz, Morten Hoyer, Simon S Lo, Umberto Ricardi, Arjun Sahgal, Rolf Stahel, Roger Stupp, Matthias Guckenberger
BACKGROUND AND PURPOSE: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment. MATERIAL AND METHODS: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK"...
February 2017: Cancer Treatment Reviews
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