keyword
https://read.qxmd.com/read/34552321/lc-ms-ms-estimation-of-rociletinib-levels-in-human-liver-microsomes-application-to-metabolic-stability-estimation
#1
JOURNAL ARTICLE
Mohamed W Attwa, Ali S Abdelhameed, Adnan A Kadi
Background: Rociletinib (CO-1686; RLC) is a new, small molecule that is orally administered to inhibit mutant-selective covalent inhibitor of most epidermal growth factor receptor (EGFR)-mutated forms, including T790M, L858R, and exon 19 deletions, but not exon 20 insertions. Non-small-cell lung cancer (NSCLC) with a gene mutation that encodes EGFR is sensitive to approved EGFR inhibitors, but usually resistance develops, which is frequently mediated by T790M EGFR mutation. RLC is an EGFR inhibitor found to be active in preclinical models of EGFR-mutated NSCLC with or without T790M...
2021: Drug Design, Development and Therapy
https://read.qxmd.com/read/33809064/a-radiobrominated-tyrosine-kinase-inhibitor-for-egfr-with-l858r-t790m-mutations-in-lung-carcinoma
#2
JOURNAL ARTICLE
Muammar Fawwaz, Kenji Mishiro, Ryuichi Nishii, Akira Makino, Yasushi Kiyono, Kazuhiro Shiba, Seigo Kinuya, Kazuma Ogawa
Activating double mutations L858R/T790M in the epidermal growth factor receptor (EGFR) region are often observed as the cause of resistance to tyrosine kinase inhibitors (TKIs). Third-generation EGFR-TKIs, such as osimertinib and rociletinib (CO-1686), was developed to target such resistance mutations. The detection of activating L858R/T790M mutations is necessary to select sensitive patients for therapy. Hence, we aimed to develop novel radiobromine-labeled CO-1686 as a positron emission tomography (PET) imaging probe for detecting EGFR L858R/T790M mutations...
March 12, 2021: Pharmaceuticals
https://read.qxmd.com/read/32599930/synthesis-and-fundamental-evaluation-of-radioiodinated-rociletinib-co-1686-as-a-probe-to-lung-cancer-with-l858r-t790m-mutations-of-epidermal-growth-factor-receptor-egfr
#3
JOURNAL ARTICLE
Muammar Fawwaz, Kenji Mishiro, Ryuichi Nishii, Izumi Sawazaki, Kazuhiro Shiba, Seigo Kinuya, Kazuma Ogawa
Rociletinib (CO-1686), a 2,4-diaminopyrimidine derivative, is a highly potent tyrosine kinase inhibitor (TKI) that acts on epidermal growth factor receptor (EGFR) with L858R/T790M mutations. We supposed radioiodinated CO-1686 would function as a useful tool for monitoring EGFR L858R/T790M mutations. To aid in patient selection before therapy with EGFR-TKIs, this study aimed to develop a 125 I-labeled derivative of CO-1686, N -{3-[(2-{[4-(4-acetylpiperazin-1-yl)-2-methoxyphenyl]amino}-5-(trifluoromethyl)pyrimidine-4-yl] amino}-5-([125 I]iodophenyl)acrylamide ([125 I]ICO1686) and evaluate its selectivity toward EGFR L858R/T790M...
June 24, 2020: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/32528828/rociletinib-co-1686-enhanced-the-efficacy-of-chemotherapeutic-agents-in-abcg2-overexpressing-cancer-cells-in-vitro-and-in-viv-o
#4
JOURNAL ARTICLE
Fanpu Zeng, Fang Wang, Zongheng Zheng, Zhen Chen, Kenneth Kin Wah To, Hong Zhang, Qian Han, Liwu Fu
Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity...
May 2020: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/30718357/novel-third-generation-egfr-tyrosine-kinase-inhibitors-and-strategies-to-overcome-therapeutic-resistance-in-lung-cancer
#5
REVIEW
Ayesha Murtuza, Ajaz Bulbul, John Paul Shen, Parissa Keshavarzian, Brian D Woodward, Fernando J Lopez-Diaz, Scott M Lippman, Hatim Husain
EGFR-activating mutations are observed in approximately 15% to 20% of patients with non-small cell lung cancer. Tyrosine kinase inhibitors have provided an illustrative example of the successes in targeting oncogene addiction in cancer and the role of tumor-specific adaptations conferring therapeutic resistance. The compound osimertinib is a third-generation tyrosine kinase inhibitor, which was granted full FDA approval in March 2017 based on targeting EGFR T790M resistance. The compound has received additional FDA approval as first-line therapy with improvement in progression-free survival by suppressing the activating mutation and preventing the rise of the dominant resistance clone...
February 15, 2019: Cancer Research
https://read.qxmd.com/read/30591099/-progress-in-non-invasive-detection-of-egfr-mutation-in-non-small-cell-lung-cancer
#6
REVIEW
Shiyang Yuan, Yeqing Zou, Junping Xie
Over the past decade, the management model of cancer patients has gradually shifted to individual mode based on molecular mutation detection. Epidermal growth factor receptor (EGFR) gene mutation is an important driving factor in non-small cell lung cancer (NSCLC). Compared with traditional chemotherapy, EGFR-targeted therapy shows significant safety and efficacy. However, not all patients with EGFR mutations are eligible for EGFR-targeted therapy, and different types of mutations often indicate different clinical outcomes, such as the sensitive mutations EGFR 19-Del, L858R, and the resistance mutation...
December 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://read.qxmd.com/read/30307719/metformin-synergistically-enhances-the-antitumor-activity-of-the-third-generation-egfr-tki-co-1686-in-lung-cancer-cells-through-suppressing-nf-%C3%AE%C2%BAb-signaling
#7
COMPARATIVE STUDY
Yong-Hong Pan, Cai-Yu Lin, Cong-Hua Lu, Li Li, Yu-Bo Wang, Heng-Yi Chen, Yong He
PURPOSE: Third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), rociletinib (CO-1686), is great efficacy against EGFR-mutated patients bearing the T790M resistance mutation. However, acquired resistance may emerge. There is a need to characterize acquired resistance mechanism(s) and to devise ways to overcome CO-1686 resistance. EXPERIMENTAL DESIGN: MTT assay, ki67 incorporation assay, transwell assay and TUNEL assay were employed to analyze the effects of metformin to reverse CO-1686 resistance in vitro...
December 2018: Clinical Respiratory Journal
https://read.qxmd.com/read/28712979/clinical-implications-of-the-t790m-mutation-in-disease-characteristics-and-treatment-response-in-patients-with-epidermal-growth-factor-receptor-egfr-mutated-non-small-cell-lung-cancer-nsclc
#8
JOURNAL ARTICLE
Daria Gaut, Myung Shin Sim, Yuguang Yue, Brian R Wolf, Phillip A Abarca, James M Carroll, Jonathan W Goldman, Edward B Garon
BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI...
January 2018: Clinical Lung Cancer
https://read.qxmd.com/read/27252416/heterogeneous-mechanisms-of-primary-and-acquired-resistance-to-third-generation-egfr-inhibitors
#9
JOURNAL ARTICLE
Sandra Ortiz-Cuaran, Matthias Scheffler, Dennis Plenker, Llona Dahmen, Andreas H Scheel, Lynnette Fernandez-Cuesta, Lydia Meder, Christine M Lovly, Thorsten Persigehl, Sabine Merkelbach-Bruse, Marc Bos, Sebastian Michels, Rieke Fischer, Kerstin Albus, Katharina König, Hans-Ulrich Schildhaus, Jana Fassunke, Michaela A Ihle, Helen Pasternack, Carina Heydt, Christian Becker, Janine Altmüller, Hongbin Ji, Christian Müller, Alexandra Florin, Johannes M Heuckmann, Peter Nuernberg, Sascha Ansén, Lukas C Heukamp, Johannes Berg, William Pao, Martin Peifer, Reinhard Buettner, Jürgen Wolf, Roman K Thomas, Martin L Sos
PURPOSE: To identify novel mechanisms of resistance to third-generation EGFR inhibitors in patients with lung adenocarcinoma that progressed under therapy with either AZD9291 or rociletinib (CO-1686). EXPERIMENTAL DESIGN: We analyzed tumor biopsies from seven patients obtained before, during, and/or after treatment with AZD9291 or rociletinib (CO-1686). Targeted sequencing and FISH analyses were performed, and the relevance of candidate genes was functionally assessed in in vitro models...
October 1, 2016: Clinical Cancer Research
https://read.qxmd.com/read/26747242/assessment-of-egfr-mutation-status-in-matched-plasma-and-tumor-tissue-of-nsclc-patients-from-a-phase-i-study-of-rociletinib-co-1686
#10
JOURNAL ARTICLE
Chris Karlovich, Jonathan W Goldman, Jong-Mu Sun, Elaina Mann, Lecia V Sequist, Krzysztof Konopa, Wei Wen, Philipp Angenendt, Leora Horn, David Spigel, Jean-Charles Soria, Benjamin Solomon, D Ross Camidge, Shirish Gadgeel, Cloud Paweletz, Lin Wu, Sean Chien, Patrick O'Donnell, Shannon Matheny, Darrin Despain, Lindsey Rolfe, Mitch Raponi, Andrew R Allen, Keunchil Park, Heather Wakelee
PURPOSE: The evaluation of plasma testing for the EGFR resistance mutation T790M in NSCLC patients has not been broadly explored. We investigated the detection of EGFR activating and T790M mutations in matched tumor tissue and plasma, mostly from patients with acquired resistance to first-generation EGFR inhibitors. EXPERIMENTAL DESIGN: Samples were obtained from two studies, an observational study and a phase I trial of rociletinib, a mutant-selective inhibitor of EGFR that targets both activating mutations and T790M...
May 15, 2016: Clinical Cancer Research
https://read.qxmd.com/read/26508839/dacomitinib-in-lung-cancer-a-lost-generation-egfr-tyrosine-kinase-inhibitor-from-a-bygone-era
#11
REVIEW
Sai-Hong Ignatius Ou, Ross A Soo
EGFR tyrosine-kinase inhibitors (TKIs) have now been firmly established as the first-line treatment for non-small-cell lung cancer (NSCLC) patients harboring activating EGFR mutations, based on seven prospective randomized Phase III trials. However, despite significantly improved overall response rate and improved median progression-free survival when compared to platinum-doublet chemotherapy, EGFR-mutant NSCLC patients treated with EGFR TKIs invariably progress due to the emergence of acquired resistances, with the gatekeeper T790M mutation accounting for up to 60% of the resistance mechanisms...
2015: Drug Design, Development and Therapy
https://read.qxmd.com/read/25923550/rociletinib-in-egfr-mutated-non-small-cell-lung-cancer
#12
RANDOMIZED CONTROLLED TRIAL
Lecia V Sequist, Jean-Charles Soria, Jonathan W Goldman, Heather A Wakelee, Shirish M Gadgeel, Andrea Varga, Vassiliki Papadimitrakopoulou, Benjamin J Solomon, Geoffrey R Oxnard, Rafal Dziadziuszko, Dara L Aisner, Robert C Doebele, Cathy Galasso, Edward B Garon, Rebecca S Heist, Jennifer Logan, Joel W Neal, Melody A Mendenhall, Suzanne Nichols, Zofia Piotrowska, Antoinette J Wozniak, Mitch Raponi, Chris A Karlovich, Sarah Jaw-Tsai, Jeffrey Isaacson, Darrin Despain, Shannon L Matheny, Lindsey Rolfe, Andrew R Allen, D Ross Camidge
BACKGROUND: Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M. METHODS: In this phase 1-2 study, we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor...
April 30, 2015: New England Journal of Medicine
1
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.