keyword
MENU ▼
Read by QxMD icon Read
search

Egfr-tki resistance

keyword
https://www.readbyqxmd.com/read/29449326/fatty-acid-synthase-mediates-egfr-palmitoylation-in-egfr-mutated-non-small-cell-lung-cancer
#1
Azhar Ali, Elena Levantini, Jun Ting Teo, Julian Goggi, John G Clohessy, Chan Shuo Wu, Leilei Chen, Henry Yang, Indira Krishnan, Olivier Kocher, Junyan Zhang, Ross A Soo, Kishore Bhakoo, Tan Min Chin, Daniel G Tenen
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug...
February 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29435131/pd-l1-confers-resistance-to-egfr-mutation-independent-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-via-upregulation-of-yap1-expression
#2
Jai-Nien Tung, Po-Lin Lin, Yao-Chen Wang, De-Wei Wu, Chi-Yi Chen, Huei Lee
Programmed death ligand (PD-L1) expression was associated with tumor immune escape and subsequent poor prognosis in non-small cell lung cancer (NSCLC). This expression was higher in patients with EGFR-mutated NSCLC tumors than in those with EGFR-wild-type (WT) NSCLC tumors. We therefore hypothesized that poor prognosis mediated by higher PD-L1 may be partially through conferring resistance to tyrosine kinase inhibitor (TKI) in NSCLC regardless of EGFR mutation. The change in PD-L1 expression following gene manipulation corresponded with changes in expression of HIF-1α and YAP1...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29433983/common-co-activation-of-axl-and-cdcp1-in-egfr-mutation-positive-non-smallcell-lung-cancer-associated-with-poor-prognosis
#3
Niki Karachaliou, Imane Chaib, Andres Felipe Cardona, Jordi Berenguer, Jillian Wilhelmina Paulina Bracht, Jie Yang, Xueting Cai, Zhigang Wang, Chunping Hu, Ana Drozdowskyj, Carles Codony Servat, Jordi Codony Servat, Masaoki Ito, Ilaria Attili, Erika Aldeguer, Ana Gimenez Capitan, July Rodriguez, Leonardo Rojas, Santiago Viteri, Miguel Angel Molina-Vila, Sai-Hong Ignatius Ou, Morihito Okada, Tony S Mok, Trever G Bivona, Mayumi Ono, Jean Cui, Santiago Ramón Y Cajal, Peng Cao, Rafael Rosell
Epidermal growth factor receptor (EGFR)-mutation-positive non-smallcell lung cancer (NSCLC) is incurable, despite high rates of response to EGFR tyrosine kinase inhibitors (TKIs). We investigated receptor tyrosine kinases (RTKs), Src family kinases and focal adhesion kinase (FAK) as genetic modifiers of innate resistance in EGFR-mutation-positive NSCLC. We performed gene expression analysis in two cohorts (Cohort 1 and Cohort 2) of EGFR-mutation-positive NSCLC patients treated with EGFR TKI. We evaluated the efficacy of gefitinib or osimertinib with the Src/FAK/Janus kinase 2 (JAK2) inhibitor, TPX0005 in vitro and in vivo...
February 5, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29425688/osimertinib-resistance-in-non-small-cell-lung-cancer-mechanisms-and-therapeutic-strategies
#4
Zheng-Hai Tang, Jin-Jian Lu
Given the successful identification of epidermal growth factor receptor EGFR T790M, the third-generation EGFR tyrosine kinase inhibitor (TKI), osimertinib (OSI, AZD9291), was developed to target EGFR T790M mutation. OSI was approved for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR T790M mutation. However, the disease would progress after the patient received OSI treatment for approximately 10 months. Resistance mechanisms to OSI, such as additional mutation of EGFR and alternative kinase activation, were recently identified, and some novel therapeutic strategies were proposed to overcome OSI resistance...
February 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29422965/upregulation-of-bcl2-in-nsclc-with-acquired-resistance-to-egfr-tki
#5
Hio Teng Cheong, Fei Xu, Chi Tung Choy, Connie Wun Chun Hui, Tony Shu Kam Mok, Chi Hang Wong
Lung cancer has the highest incidence and mortality rate worldwide among all malignancy-associated mortalities, of which non-small cell lung cancer accounts for 80% of all cases. Resistance against epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) develops following 8-12 months of disease progression, and is a critical issue. HCC827 cell lines with resistance to EGFR-TKIs were successfully screened. The half maximal inhibitory concentration values were 1,000-fold higher than the values for the parental HCC827 cell line, thereby demonstrating cross-resistance against the same family of TKIs...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29421153/nuclear-translocation-of-igf1r-by-intracellular-amphiregulin-contributes-to-the-resistance-of-lung-tumour-cells-to-egfr-tki
#6
Marie Guerard, Thomas Robin, Pascal Perron, Anne-Sophie Hatat, Laurence David-Boudet, Laetitia Vanwonterghem, Benoit Busser, Jean-Luc Coll, Sylvie Lantuejoul, Beatrice Eymin, Amandine Hurbin, Sylvie Gazzeri
Many Receptor Tyrosine Kinases translocate from the cell surface to the nucleus in normal and pathological conditions, including cancer. Here we report the nuclear expression of insulin-like growth factor-1 receptor (IGF1R) in primary human lung tumours. Using lung cancer cell lines and lung tumour xenografts, we demonstrate that the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib induces the nuclear accumulation of IGF1R in mucinous lung adenocarcinoma by a mechanism involving the intracellular re-localization of the growth factor amphiregulin...
February 5, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29416720/targeting-the-golgi-apparatus-to-overcome-acquired-resistance-of-non-small-cell-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitors
#7
Yoshimi Ohashi, Mutsumi Okamura, Ryohei Katayama, Siyang Fang, Saki Tsutsui, Akinobu Akatsuka, Mingde Shan, Hyeong-Wook Choi, Naoya Fujita, Kentaro Yoshimatsu, Isamu Shiina, Takao Yamori, Shingo Dan
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) were demonstrated to provide survival benefit in patients with non-small cell lung cancer (NSCLC) harboring activating mutations of EGFR; however, emergence of acquired resistance to EGFR-TKIs has been shown to cause poor outcome. To overcome the TKI resistance, drugs with different mode of action are required. We previously reported that M-COPA (2-methylcoprophilinamide), a Golgi disruptor, suppressed the growth of gastric cancers overexpressing receptor tyrosine kinases (RTKs) such as hepatocyte growth factor receptor (MET) via downregulating their cell surface expression...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29413049/high-cripto-1-and-low-mir-205-expression-levels-as-prognostic-markers-in-early-stage-non-small-cell-lung-cancer
#8
Kang-Seo Park, Yong Wha Moon, Mark Raffeld, Dae Ho Lee, Yisong Wang, Giuseppe Giaccone
OBJECTIVES: Cripto-1 (CR-1) plays a critical role in the activation of SMAD, SRC, and epithelial-to-mesenchymal transition (EMT) pathways and has been shown to be prognostic in several cancer types. In addition, we showed that CR-1 renders EGFR-mutated NSCLC cells resistant to EGFR-TKI through the activation of SRC and EMT via miR-205 downregulation. This study aimed to investigate the correlation between expression of CR-1 and miR-205 and prognosis of NSCLC patients with or without EGFR mutations...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29409466/frequency-of-the-acquired-resistant-mutation-t790%C3%A2-m-in-non-small-cell-lung-cancer-patients-with-active-exon-19del-and-exon-21-l858r-a-systematic-review-and-meta-analysis
#9
Zan-Feng Wang, Sheng-Xiang Ren, Wei Li, Guang-Hui Gao
BACKGROUND: Although EGFR-TKI is the preferred treatment for NSCLC patients with sensitive mutations, subsequent drug resistance is almost inevitable. The specific mechanisms of EGFR-TKI drug resistance can be identified through repeat biopsy. METHODS: To better understand the clinical characteristics of TKI resistance in NSCLC patients, we retrospectively reviewed studies of acquired TKI drug resistance using repeat biopsy from the last decade. The relevant literature was retrieved from January 2005 to August 2015 in the databases Medline and Embase...
February 6, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29404164/treatment-after-first-generation-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-resistance-in-non-small-cell-lung-cancer
#10
REVIEW
Seher Nazlı Kazaz, İlhan Öztop
Systemic treatment is the basic treatment approach to advanced-stage non-small-cell lung cancer (NSCLC), and chemotherapy and targeted treatments are commonly employed in these patients. Recently, positive results achieved with immunotherapy have led to a growing number of treatment options and prolonged survival time. Today, specific tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and the TKI crizotinib, which targets anaplastic lymphoma kinase gene rearrangement, have become the standard treatment among targeted therapies for patients with sensitive molecular anomalies...
July 2017: Turkish Thoracic Journal
https://www.readbyqxmd.com/read/29399169/histone-deacetylation-as-opposed-to-promoter-methylation-results-in-epigenetic-bim-silencing-and-resistance-to-egfr-tki-in-nsclc
#11
Mingchuan Zhao, Yishi Zhang, Jiayu Li, Xuefei Li, Ningning Cheng, Qi Wang, Weijing Cai, Chao Zhao, Yayi He, Jianhua Chang, Caicun Zhou
Drug resistance remains a major challenge in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Bcl-2-like protein 11 (BIM), a B-cell lymphoma 2 family pro-apoptotic protein, is a prime target for specific anti-cancer therapeutics. However, the epigenetic regulation of BIM in non-small cell lung cancer (NSCLC) cell lines and patients with NSCLC in association with EGFR-TKI resistance requires investigation. Methylation-specific PCR (MSP), pyrosequencing, and nested quantitative (q)-MSP were conducted to explore the methylation status of BIM in NSCLC cell lines...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29393480/sensitivity-to-chemotherapeutics-of-nsclc-cells-with-acquired-resistance-to-egfr-tkis-is-mediated-by-t790m-mutation-or-epithelial-mesenchymal-transition
#12
Juan Zhou, Qiaoting Hu, Xi Zhang, Jihua Zheng, Bo Xie, Zhiyong Xu, Weimin Zhang
Chemotherapy is one of the methods to treat patients with non-small cell lung cancer (NSCLC) developing resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib. Previous studies revealed that the sensitivity to chemotherapy may depend on different cellular mechanisms of acquired EGFR-TKIs resistance. Thus, the present study aimed to investigate the sensitivity of distinct gefitinib-resistant NSCLC cell lines to chemotherapy in order to help select effective treatment regimens for patients with EGFR-TKI resistance...
February 1, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29388752/iron-oxide-nanoparticles-synergize-with-erlotinib-to-suppress-refractory-non-small-cell-lung-cancer-cell-proliferation-through-the-inhibition-of-erbb-pi3k-akt-and-pten-activation
#13
Meili Zhang, Buqing Sai, Pengfei Cao, Zheng Li, Liyang Zhang, Cijun Shuai, Xinye Wang, Jia Wang, Guiyuan Li, Juanjuan Xiang, Jingqun Tang
Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib, are currently approved for the management of NSCLC. However, primary and acquired resistances to EGFR-TKIs are the major obstacles in the treatment of NSCLC. These resistances have been associated with the development of secondary mutations in EGFR or continued oncogenic signaling despite TKI treatment. In this study, NSCLC cells with wild-type EGFR, A549, H460, H358, H157 which do not respond to EGFR-TKIs, were used...
April 2017: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/29386539/met-or-nras-amplification-is-an-acquired-resistance-mechanism-to-the-third-generation-egfr-inhibitor-naquotinib
#14
Kiichiro Ninomiya, Kadoaki Ohashi, Go Makimoto, Shuta Tomida, Hisao Higo, Hiroe Kayatani, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura
As a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimeritnib is the standard treatment for patients with non-small cell lung cancer harboring the EGFR T790M mutation; however, acquired resistance inevitably develops. Therefore, a next-generation treatment strategy is warranted in the osimertinib era. We investigated the mechanism of resistance to a novel EGFR-TKI, naquotinib, with the goal of developing a novel treatment strategy. We established multiple naquotinib-resistant cell lines or osimertinib-resistant cells, two of which were derived from EGFR-TKI-naïve cells; the others were derived from gefitinib- or afatinib-resistant cells harboring EGFR T790M...
January 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29385152/intratumoral-heterogeneity-characterized-by-pretreatment-pet-in-non-small-cell-lung-cancer-patients-predicts-progression-free-survival-on-egfr-tyrosine-kinase-inhibitor
#15
Sehhoon Park, Seunggyun Ha, Se-Hoon Lee, Jin Chul Paeng, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo
Intratumoral heterogeneity has been suggested to be an important resistance mechanism leading to treatment failure. We hypothesized that radiologic images could be an alternative method for identification of tumor heterogeneity. We tested heterogeneity textural parameters on pretreatment FDG-PET/CT in order to assess the predictive value of target therapy. Recurred or metastatic non-small cell lung cancer (NSCLC) subjects with an activating EGFR mutation treated with either gefitinib or erlotinib were reviewed...
2018: PloS One
https://www.readbyqxmd.com/read/29378193/ppargamma-agonists-sensitize-pten-deficient-resistant-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitors-by-inducing-autophagy
#16
Kenneth K W To, William K K Wu, Herbert H F Loong
We aimed to develop novel drug combination strategy to overcome drug resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in the treatment of non-small cell lung cancer (NSCLC). Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor, which upon activation upregulates phosphatase and tensin homolog (PTEN) to inhibit cell signaling downstream of PI3K to mediate apoptosis. To this end, PTEN loss is a known mechanism contributing to resistance to EGFR TKIs...
January 30, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29377179/targeting-egfrl858r-t790m-and-egfrl858r-t790m-c797s-resistance-mutations-in-nsclc-current-developments-in-medicinal-chemistry
#17
REVIEW
Xiaoyun Lu, Lei Yu, Zhang Zhang, Xiaomei Ren, Jeff B Smaill, Ke Ding
Both the first-generation reversible epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib and the second-generation covalent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) afatinib have significantly improved the survival of non-small-cell lung cancer (NSCLC) patients with activating EGFR mutations. However, a secondary EGFRT790M mutation leads to the clinically acquired resistance to the first- and second-generation EGFR-TKIs drugs. A number of the third-generation wild-type sparing EGFR inhibitors, for example, WZ4002, CO1686, AZD9291, HM61713, EGF816, ASP8173, and PF0674775, have been developed, among which AZD9291 has been approved by US FDA for the treatment of NSCLC patients with EGFRT790M ...
January 26, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29374157/targeting-ehmt2-reverses-egfr-tki-resistance-in-nsclc-by-epigenetically-regulating-the-pten-akt-signaling-pathway
#18
Lihui Wang, Xiaoyu Dong, Yong Ren, Juanjuan Luo, Pei Liu, Dongsheng Su, Xiaojun Yang
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). Epigenetic alterations have been shown to be involved in NSCLC oncogenesis; however, their function in EGFR-TKI resistance remains uncharacterized. Here, we found that an EHMT2 inhibitor, UNC0638, can significantly inhibit cell growth and induce apoptosis in EGFR-TKI-resistant NSCLC cells. Additionally, we also found that EHMT2 expression and enzymatic activity levels were elevated in EGFR-TKI-resistant NSCLC cells...
January 26, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29363250/osimertinib-in-patients-with-egfr-t790m-advanced-non-small-cell-lung-cancer-selected-using-cytology-samples
#19
Katsuyuki Kiura, Kiyotaka Yoh, Nobuyuki Katakami, Naoyuki Nogami, Kazuo Kasahara, Toshiaki Takahashi, Isamu Okamoto, Mireille Cantarini, Rachel Hodge, Hirohiko Uchida
Osimertinib is a potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR-TKI sensitizing (EGFRm) and T790M resistance mutations. The primary objective of the cytology cohort in the AURA study was to investigate safety and efficacy of osimertinib in pretreated Japanese patients with EGFR T790M mutation-positive NSCLC, with screening EGFR T790M mutation status determined from cytology samples. The cytology cohort was included in the Phase I dose expansion component of the AURA study. Patients were enrolled based on a positive result of T790M by using cytology samples, and received osimertinib 80 mg in tablet form once daily until disease progression or until clinical benefit was no longer observed at the discretion of the investigator...
January 24, 2018: Cancer Science
https://www.readbyqxmd.com/read/29354805/current-progress-and-outcomes-of-clinical-trials-on-using-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-therapy-in-non-small-cell-lung-cancer-patients-with-brain-metastases
#20
Ling-Ling Kong, Lin-Lin Wang, Li-Gang Xing, Jin-Ming Yu
Non-small cell lung cancer (NSCLC) continues to be one of the major causes of cancer-related deaths worldwide, and brain metastases are the major cause of death in NSCLC patients. With recent advances in understanding the underlying molecular mechanism of NSCLC development and progression, mutations in epidermal growth factor receptor (EGFR) have been recognized as a key predictor of therapeutic sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Using EGFR-TKI alone or in combination with standard treatments such as whole-brain radiotherapy and surgery has been an effective strategy for the management of brain metastasis...
December 2017: Chronic diseases and translational medicine
keyword
keyword
32713
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

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"