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https://www.readbyqxmd.com/read/28193771/ceritinib-bests-chemo-for-untreated-alk-nsclc
#1
(no author information available yet)
Patients with ALK-positive non-small cell lung cancer may soon have a new first-line treatment option in ceritinib, which outperformed chemotherapy in a phase III study. However, toxicity issues remain a problem for ceritinib, and another next-generation ALK inhibitor, alectinib, is more likely to become the drug of choice for untreated patients.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28176528/lc-ms-ms-determination-of-alectinib-and-its-major-human-metabolite-m4-in-human-urine-prevention-of-nonspecific-binding
#2
Katja Heinig, Denis Herzog, Luca Ferrari, Daniela Fraier, Kazuhiro Miya, Peter N Morcos
AIM: Alectinib (Alecensa(®)) is an anaplastic lymphoma kinase inhibitor for the treatment of anaplastic lymphoma kinase positive non-small-cell lung cancer, and M4 is its major pharmacologically active metabolite. To characterize the pharmacokinetics and excretion of alectinib and M4 in human urine, a bioanalytical method was required. RESULTS: An LC-MS/MS method using supported liquid extraction was developed for the determination of alectinib and M4 in human urine over the concentration range 0...
February 8, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28167572/an-oncogenic-alk-fusion-and-an-rras-mutation-in-kras-mutation-negative-pancreatic-ductal-adenocarcinoma
#3
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/28101031/alectinib-induced-erythema-multiforme-and-successful-rechallenge-with-alectinib-in-a-patient-with-anaplastic-lymphoma-kinase-rearranged-lung-cancer
#4
Tatsuo Kimura, Junko Sowa-Osako, Toshiyuki Nakai, Ayako Ohyama, Tomoya Kawaguchi, Daisuke Tsuruta, Masahiko Ohsawa, Kazuto Hirata
BACKGROUND: Alectinib is an oral drug developed for the treatment of patients with fusion gene encoding echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we present the case of a patient treated with alectinib who developed a hypersensitivity reaction with successful rechallenge treatment. CASE PRESENTATION: A 39-year-old woman who was a passive smoker was referred to Osaka City University Hospital for the evaluation of a skin event caused by treatment for NSCLC with the fusion gene EML4-ALK...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28077299/anaplastic-lymphoma-kinase-alk-inhibitors-in-the-treatment-of-alk-driven-lung-cancers
#5
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/28066567/sequencing-alk-inhibitors-alectinib-in-crizotinib-resistant-patients-a-phase-2-trial-by-shaw-et-al
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28054318/treating-patients-with-alk-rearranged-non-small-cell-lung-cancer-mechanisms-of-resistance-and-strategies-to-overcome-it
#9
REVIEW
M Drizou, E A Kotteas, N Syrigos
Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases...
January 4, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28050598/alk-a-tyrosine-kinase-target-for-cancer-therapy
#10
REVIEW
Vijaykumar R Holla, Yasir Y Elamin, Ann Marie Bailey, Amber M Johnson, Beate C Litzenburger, Yekaterina B Khotskaya, Nora S Sanchez, Jia Zeng, Md Abu Shufean, Kenna R Shaw, John Mendelsohn, Gordon B Mills, Funda Meric-Bernstam, George R Simon
The anaplastic lymphoma kinase (ALK) gene plays an important physiologic role in the development of the brain and can be oncogenically altered in several malignancies, including non-small-cell lung cancer (NSCLC) and anaplastic large cell lymphomas (ALCL). Most prevalent ALK alterations are chromosomal rearrangements resulting in fusion genes, as seen in ALCL and NSCLC. In other tumors, ALK copy-number gains and activating ALK mutations have been described. Dramatic and often prolonged responses are seen in patients with ALK alterations when treated with ALK inhibitors...
January 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28039177/differential-protein-stability-and-clinical-responses-of-eml4-alkfusion-variants-to-various-alk-inhibitors-in-advanced-alk-rearranged-non-small-cell-lung-cancer
#11
C G Woo, S Seo, S W Kim, S J Jang, K S Park, J Y Song, B Lee, M W Richards, R Bayliss, D H Lee, J Choi
BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro. However, there are only limited data on the specific EML4-ALK variants and clinical responses of patients to various ALK inhibitors...
December 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27972441/a-budget-impact-analysis-to-estimate-the-cost-savings-from-alectinib-on-patients-with-anaplastic-lymphoma-kinase-alk-positive-locally-advanced-or-metastatic-non-small-cell-lung-cancer-nsclc-previously-treated-with-crizotinib
#12
P Orfanos, U Becker
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27965961/focus-on-alectinib-and-competitor-compounds-for-second-line-therapy-in-alk-rearranged-nsclc
#13
REVIEW
Phu N Tran, Samuel J Klempner
The management of anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) exemplifies the potential of a precision medicine approach to cancer care. The ALK inhibitor crizotinib has led to improved outcomes in the first- and second-line setting; however, toxicities, intracranial activity, and acquired resistance necessitated the advent of later generation ALK inhibitors. A large portion of acquired resistance to ALK inhibitors is caused by secondary mutations in the ALK kinase domain...
2016: Frontiers in Medicine
https://www.readbyqxmd.com/read/27912826/diagnosis-and-treatment-of-anaplastic-lymphoma-kinase-positive-non-small-cell-lung-cancer
#14
REVIEW
Kathryn C Arbour, Gregory J Riely
Anaplastic lymphoma kinase (ALK) gene rearrangements occur in a small portion of patients with non-small cell lung cancer (NSCLC). These gene rearrangements lead to constitutive activation of the ALK kinase and subsequent ALK-driven tumor formation. Patients with tumors harboring such rearrangements are highly sensitive to ALK inhibitors, such as crizotinib, ceritinib, and alectinib. Resistance to these kinase inhibitors occurs through several mechanisms, resulting in ongoing clinical challenges. This review summarizes the biology of ALK-positive lung cancer, methods for diagnosing ALK-positive NSCLC, current FDA-approved ALK inhibitors, mechanisms of resistance to ALK inhibition, and potential strategies to combat resistance...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27888620/identification-of-different-alk-mutations-in-a-pair-of-neuroblastoma-cell-lines-established-at-diagnosis-and-relapse
#15
Lindi Chen, Angharad Humphreys, Lisa Turnbull, Angela Bellini, Gudrun Schleiermacher, Helen Salwen, Susan L Cohn, Nick Bown, Deborah A Tweddle
Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor kinase that belongs to the insulin receptor superfamily and has previously been shown to play a role in cell proliferation, migration and invasion in neuroblastoma. Activating ALK mutations are reported in both hereditary and sporadic neuroblastoma tumours, and several ALK inhibitors are currently under clinical evaluation as novel treatments for neuroblastoma. Overall, mutations at codons F1174, R1275 and F1245 together account for ~85% of reported ALK mutations in neuroblastoma...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879019/screening-for-alk-abnormalities-in-central-nervous-system-metastases-of-non-small-cell-lung-cancer-alk-abnormalities-in-cns-metastases-of-nsclc
#16
Marcin Nicoś, Bożena Jarosz, Paweł Krawczyk, Kamila Wojas-Krawczyk, Tomasz Kucharczyk, Marek Sawicki, Juliusz Pankowski, Tomasz Trojanowski, Janusz Milanowski
Anaplastic lymphoma kinase (ALK) gene rearrangement was reported in 3-7% of primary non-small-cell lung cancer (NSCLC) and its presence is commonly associated with adenocarcinoma (AD) type and non-smoking history. ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed efficiency in patients with primary NSCLC harboring ALK gene rearrangement. Moreover, response to ALK TKIs was observed in central nervous system (CNS) metastatic lesions of NSCLC. However, there are no reports concerning the frequency of ALK rearrangement in CNS metastases...
November 23, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27867615/current-evidence-in-support-of-the-second-generation-anaplastic-lymphoma-kinase-alk-tyrosine-kinase-inhibitor-alectinib-for-the-treatment-of-non-small-cell-lung-cancer-positive-for-alk-translocation
#17
EDITORIAL
https://www.readbyqxmd.com/read/27865624/w-alk-into-the-next-stage
#18
REVIEW
Gouji Toyokawa, Takashi Seto, Mitsuhiro Takenoyama, Yukito Ichinose
In 2007, the rearrangement of anaplastic lymphoma kinase (ALK) was identified to be associated with the pathogenesis of a subset of patients with non-small-cell lung cancer (NSCLC). Surprisingly, approximately 4 years after the discovery of ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi), crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and Drug Administration. Subsequently, next-generation ALKis, such as alectinib and ceritinib, have been developed, and some of them have been applied in the clinical setting...
October 26, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27863201/pooled-analysis-of-cns-response-to-alectinib-in-two-studies-of-pretreated-patients-with-alk-positive-non-small-cell-lung-cancer
#19
Shirish M Gadgeel, Alice T Shaw, Ramaswamy Govindan, Leena Gandhi, Mark A Socinski, D Ross Camidge, Luigi De Petris, Dong-Wan Kim, Alberto Chiappori, Denis L Moro-Sibilot, Michael Duruisseaux, Lucio Crino, Tommaso De Pas, Eric Dansin, Antje Tessmer, James Chih-Hsin Yang, Ji-Youn Han, Walter Bordogna, Sophie Golding, Ali Zeaiter, Sai-Hong Ignatius Ou
Purpose Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27811184/coupling-an-eml4-alk-centric-interactome-with-rna-interference-identifies-sensitizers-to-alk-inhibitors
#20
Guolin Zhang, Hannah Scarborough, Jihye Kim, Andrii I Rozhok, Yian Ann Chen, Xiaohui Zhang, Lanxi Song, Yun Bai, Bin Fang, Richard Z Liu, John Koomen, Aik Choon Tan, James Degregori, Eric B Haura
Patients with lung cancers harboring anaplastic lymphoma kinase (ALK) gene fusions benefit from treatment with ALK inhibitors, but acquired resistance inevitably arises. A better understanding of proximal ALK signaling mechanisms may identify sensitizers to ALK inhibitors that disrupt the balance between prosurvival and proapoptotic effector signals. Using affinity purification coupled with mass spectrometry in an ALK fusion lung cancer cell line (H3122), we generated an ALK signaling network and investigated signaling activity using tyrosine phosphoproteomics...
October 18, 2016: Science Signaling
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