keyword
MENU ▼
Read by QxMD icon Read
search

Kras lung cancer

keyword
https://www.readbyqxmd.com/read/29051323/epithelial-to-mesenchymal-transition-antagonizes-response-to-targeted-therapies-in-lung-cancer-by-suppressing-bim
#1
Kyung-A Song, Matthew J Niederst, Timothy L Lochmann, Aaron N Hata, Hidenori Kitai, Jungoh Ham, Konstantinos V Floros, Mark A Hicks, Haichuan Hu, Hillary E Mulvey, Yotam Drier, Daniel A R Heisey, Mark T Hughes, Neha U Patel, Elizabeth Lockerman, Angel R Garcia, Shawn Gillepsie, Hannah L Archibald, Maria Gomez-Caraballo, Tara J Nulton, Brad Windle, Zofia Piotrowska, Sinem E Sahingur, Shirley M Taylor, Mikhail G Dozmorov, Lecia V Sequist, Bradley E Bernstein, Hiromichi Ebi, Jeffrey A Engelman, Anthony C Faber
PURPOSE: Epithelial-to-mesenchymal transition (EMT) confers resistance to a number of targeted therapies and chemotherapies. However, it has been unclear why EMT promotes resistance, thereby impairing progress to overcome it. EXPERIMENTAL DESIGN: We have developed several models of EMT-mediated resistance to EGFR inhibitors (EGFRi) in EGFR mutant lung cancers to evaluate a novel mechanism of EMT-mediated resistance. Results: We observed that mesenchymal EGFR mutant lung cancers are resistant to EGFRi-induced apoptosis via insufficient expression of BIM, preventing cell death despite potent suppression of oncogenic signaling following EGFRi treatment...
October 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29050231/a-phase-i-study-of-foretinib-plus-erlotinib-in-patients-with-previously-treated-advanced-non-small-cell-lung-cancer-canadian-cancer-trials-group-ind-196
#2
Natasha B Leighl, Ming-Sound Tsao, Geoffrey Liu, Dongsheng Tu, Cheryl Ho, Frances A Shepherd, Nevin Murray, John R Goffin, Garth Nicholas, Shingo Sakashita, Zhuo Chen, Lucia Kim, Jean Powers, Lesley Seymour, Glenwood Goss, Penelope A Bradbury
PURPOSE: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance. This dose escalation study combined foretinib and erlotinib in advanced pretreated NSCLC patients. EXPERIMENTAL DESIGN: The primary endpoint was to define the RP2D of foretinib plus erlotinib as continuous oral daily dosing. Secondary objectives included safety, pharmacokinetics, response and potential biomarkers of response including EGFR, KRAS genotype, MET, AXL expression, and circulating HGF levels...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29047229/enhanced-inflammation-and-attenuated-tumor-suppressor-pathways-are-associated-with-oncogene-induced-lung-tumors-in-aged-mice
#3
Neha Parikh, Ryan L Shuck, Mihai Gagea, Lanlan Shen, Lawrence A Donehower
Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic Kras(G12D) was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activation of Kras(G12D) in old mice resulted in shorter survival and development of higher-grade lung tumors. Six weeks after Kras(G12D) activation, old lung tissues contained higher numbers of adenomas than their young tissue counterparts...
October 18, 2017: Aging Cell
https://www.readbyqxmd.com/read/29045535/select-2-a-phase-ii-double-blind-randomised-placebo-controlled-study-to-assess-the-efficacy-of-selumetinib-plus-docetaxel-as-a-second-line-treatment-for-patients-with-advanced-or-metastatic-non-small-cell-lung-cancer
#4
J C Soria, A Fülöp, C Maciel, J R Fischer, G Girotto, S Lago, E Smit, G Ostoros, W E E Eberhardt, P Lishkovska, S Lovick, G Mariani, A McKeown, E Kilgour, P Smith, K Bowen, A Kohlmann, D J Carlile, P A Jänne
Background: Combination of selumetinib plus docetaxel provided clinical benefit in a previous Phase II trial for patients with KRAS-mutant advanced non-small cell lung cancer (NSCLC). The Phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC. Patients and methods: Patients who had disease progression after first-line anti-cancer therapy were randomised (2:2:1) to selumetinib 75 mg BID plus docetaxel 60 mg/m2 or 75 mg/m2 (SEL+DOC 60; SEL+DOC 75), or placebo plus docetaxel 75 mg/m2 (PBO+DOC 75)...
October 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29036791/globo-h-expression-is-associated-with-driver-mutations-and-pd-l1-expressions-in-stage-i-non-small-cell-lung-cancer
#5
Ching-Yao Yang, Mong-Wei Lin, Yih-Leong Chang, Chen-Tu Wu
BACKGROUND: Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. OBJECTIVES: We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1)...
September 29, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29030351/keap1-loss-drives-kras-mutant-lung-cancer-and-glutaminolysis-dependency
#6
(no author information available yet)
Loss of Keap1 hyperactivates NRF2 to induce glutaminolysis-dependent Kras-driven lung cancer.
October 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29021381/activation-of-fak-and-src-mediates-acquired-sorafenib-resistance-in-a549-human-lung-adenocarcinoma-xenografts
#7
Qingyu S Zhou, Xiaofang Guo, Riya Choksi
Despite encouraging clinical results with sorafenib monotherapy in patients with KRAS-mutant non-small cell lung cancer (NSCLC), the overall survival benefit of this drug is limited by the inevitable development of acquired resistance. The exact mechanism underlying acquired sorafenib resistance in KRAS-mutant NSCLC is unclear. In this study, the mechanism of acquired sorafenib resistance was explored using a biologically relevant xenograft model, which was established by using the A549 human lung adenocarcinoma cell line and an in-vivo derived sorafenib-resistant A549 subline (A549/SRFres)...
October 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29018205/genetic-status-of-kras-modulates-the-role-of-neuropilin-1-in-tumorigenesis
#8
Sneha Vivekanandhan, Lijuan Yang, Ying Cao, Engfeng Wang, Shamit K Dutta, Anil K Sharma, Debabrata Mukhopadhyay
Neuropilin-1 (NRP1), a non-tyrosine kinase receptor, is overexpressed in many cancers including pancreatic and lung cancers. Inhibition of NRP1 expression, however, has differing pro-tumor vs. anti-tumor effects, depending on the cancer types. To understand the differential role of NRP1 in tumorigenesis process, we utilized cells from two different cancer types, pancreatic and lung, each containing either wild type KRAS (KRAS (wt)) or mutant KRAS (KRAS (mt)). Inhibition of NRP1 expression by shRNA in both pancreatic and lung cancer cells containing dominant active KRAS (mt) caused increased cell viability and tumor growth...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28989040/molecular-adequacy-of-image-guided-rebiopsies-for-molecular-retesting-in-advanced-non-small-cell-lung-cancer-a-single-centre-experience
#9
Nadza Tokaca, Sarah Barth, Mary O'Brien, Jaishree Bhosle, Nicos Fotiadis, Andrew Wotherspoon, Lisa Thompson, Sanjay Popat
INTRODUCTION: In the era of biomarker-driven systemic therapy for advanced non-small cell lung cancer (NSCLC), the role of routine repeated biopsies for decision-making, outside EGFR mutant disease, remains unproven. We report our centre's experience of safety and adequacy for molecular retesting of tumour material obtained from image-guided lung rebiopsies in NSCLC. METHODS: We performed a retrospective case-note analysis of patients undergoing image-guided lung rebiopsies at a single cancer centre between 2011-14...
October 5, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28984774/a-case-report-of-tongue-metastasis-from-lung-squamous-cell-carcinoma-and-literature-review
#10
REVIEW
Xiaolong Cheng, Zhenli Hu, Yipin Han, Chong Bai
RATIONALE: Tongue metastasis from lung cancer is extremely rare, and the prognosis of these patients is rather poor. PATIENT CONCERS: A 56-year-old man was found a 4-cm cavity lesion in the left upper lobe, which was initially misdiagnosed as tuberculosis. DIAGNOSES: A case of lung squamous cell carcinoma that metastasized to the base of a patient's tongue. INTERVATIONS: We send the biopsy of the lung and the tongue lesions for gene sequencing...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28982179/a-study-of-pd-l1-expression-in-kras-mutant-non-small-cell-lung-cancer-cell-lines-exposed-to-relevant-targeted-treatments
#11
Anna Minchom, Parames Thavasu, Zai Ahmad, Adam Stewart, Alexandros Georgiou, Mary E R O'Brien, Sanjay Popat, Jaishree Bhosle, Timothy A Yap, Johann de Bono, Udai Banerji
We investigated PD-L1 changes in response to MEK and AKT inhibitors in KRAS mutant lung adenocarcinoma (adeno-NSCLC). PD-L1 expression was quantified using immunofluorescence and co-culture with a jurkat cell-line transfected with NFAT-luciferase was used to study if changes in PD-L1 expression in cancer cell lines were functionally relevant. Five KRAS mutant cell lines with high PD-L1 expression (H441, H2291, H23, H2030 and A549) were exposed to GI50 inhibitor concentrations of a MEK inhibitor (trametinib) and an AKT inhibitor (AZD5363) for 3 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28979819/kras-mutation-status-is-highly-homogeneous-between-areas-of-the-primary-tumor-and-the-corresponding-metastasis-of-colorectal-adenocarcinomas-one-less-problem-in-patient-care
#12
Mariana Petaccia de Macedo, Fernanda M Melo, Heber Salvador C Ribeiro, Marcio C Marques, Luciane T Kagohara, Maria Dirlei Begnami, Julio C Neto, Júlia S Ribeiro, Fernando A Soares, Dirce M Carraro, Isabela W Cunha
Background: Mutations in KRAS are negative predictors of the response to anti-EGFR therapies in the treatment of metastatic colorectal cancer. Yet, the ideal tissue to test for KRAS mutation-primary or metastatic-remains unknown, as is the validity of testing only 1 area of the primary tumor. The aim of this study was to determine the heterogeneity of KRAS mutational status between areas of the primary lesion and between paired primary CRC and the corresponding lymph node (LN), liver, and lung metastasis with a high-sensitivity sequencing method...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28979142/the-non-small-cell-lung-cancer-egfr-extracellular-domain-mutation-m277e-is-oncogenic-and-drug-sensitive
#13
Su Yu, Yang Zhang, Yunjian Pan, Chao Cheng, Yihua Sun, Haiquan Chen
PURPOSE: To identify novel oncogenic mutations in non-small cell lung cancer patient specimens that lack mutations in known targetable genes ("pan-negative" patients). METHODS: Comprehensive mutational analyses were performed on 1,356 lung adenocarcinoma specimens. In this cohort of patients, common lung cancer oncogenic driver mutations were detected in the epidermal growth factor receptor (EGFR) kinase domain, the human epidermal growth factor receptor 2 kinase domain, as well as the KRAS, BRAF, ALK, ROS1 and RET genes...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28978720/gamma-secretase-inhibition-by-bms-906024-enhances-efficacy-of-paclitaxel-in-lung-adenocarcinoma
#14
Katherine M Morgan, Bruce S Fischer, Francis Y Lee, Jamie J Shah, Joseph R Bertino, Jeffrey Rosenfeld, Amartya Singh, Hossein Khiabanian, Sharon R Pine
Notch signaling is aberrantly activated in approximately one third of non-small cell lung cancers (NSCLC). We characterized the interaction between BMS-906024, a clinically relevant Notch gamma secretase inhibitor (GSI), and front-line chemotherapy in preclinical models of NSCLC. Chemosensitivity assays were performed on 14 human NSCLC cell lines. There was significantly greater synergy between BMS-906024 and paclitaxel than BMS-906024 and cisplatin (mean CI value = 0.54 and 0.85, respectively, P = 0.01). On an extended panel of 31 NSCLC cell lines, 25 of which were adenocarcinoma, the synergy between BMS-906024 and paclitaxel was significantly greater in KRAS- and BRAF-wildtype than KRAS- or BRAF-mutant cells (mean CI = 0...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28978051/mutational-status-of-tp53-defines-the-efficacy-of-wee1-inhibitor-azd1775-in-kras-mutant-non-small-cell-lung-cancer
#15
Bo Mi Ku, Yeon-Hee Bae, Jiae Koh, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
KRAS is frequently mutated in non-small cell lung cancer (NSCLC). However, direct targeting of KRAS has proven to be challenging, and inhibition of KRAS effectors has resulted in limited clinical efficacy. Wee1 kinase is an important regulator of the G2 checkpoint and is overexpressed in various cancers. Inhibition of Wee1 exerts anticancer effects as a monotherapy or in combination with DNA-damaging agents when cancer cells harbor TP53 mutations. However, its role in KRAS-mutant NSCLC, especially as a single agent, has not been explored...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977762/lung-cancer-heterogeneity-and-new-strategies-for-drug-therapy
#16
Diane C Wang, William Wang, Bijun Zhu, Xiangdong Wang
Lung cancer heterogeneity plays an important role in the development of drug resistance. Comprehensive molecular characterizations of lung cancer can describe hereditary and somatic gene changes, mutation, and heterogeneity. We discuss heterogeneity specificity, characterization, and roles of PIK3CD, TP53, and KRAS, as well as target-driven therapies and strategies applied in clinical trials based on a proposed precise self-validation system. The system is a specifically selected strategy of treatment for patients with cancer gene mutations and heterogeneity based on gene sequencing, following validation of the strategies in the patient's own cancer cells or in patientderived xenografts using their own cancer cells isolated during surgery or biopsies...
October 4, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28976703/the-effects-of-nrf2-modulation-on-the-initiation-and-progression-of-chemically-and-genetically-induced-lung-cancer
#17
Shasha Tao, Montserrat Rojo de la Vega, Eli Chapman, Aikseng Ooi, Donna D Zhang
Targeting the transcription factor NRF2 has been recognized as a feasible strategy for cancer prevention and treatment, but many of the mechanistic details underlying its role in cancer development and progression are lacking. Therefore, careful mechanistic studies of the NRF2 pathway in cancer initiation and progression are needed to identify which therapeutic avenue-activation or inhibition-is appropriate in a given context. Moreover, while numerous reports confirm the protective effect of NRF2 activation against chemical carcinogenesis little is known of its role in cancer arising from spontaneous mutations...
October 4, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28971587/concurrent-ros1-gene-rearrangement-and-kras-mutation-in-lung-adenocarcinoma-a-case-report-and-literature-review
#18
You-Cai Zhu, Xue-Ping Lin, Xiao-Feng Li, Li-Xin Wu, Hua-Fei Chen, Wen-Xian Wang, Chun-Wei Xu, Jian-Fa Shen, Jian-Guo Wei, Kai-Qi Du
Lung adenocarcinomas with gene rearrangement in the receptor tyrosine kinase ROS1 have emerged as a rare molecular subtype. Although these lung adenocarcinomas respond to ROS1tyrosine kinase inhibitors, many patients ultimately acquire resistance. ROS1gene rearrangement is generally mutually exclusive with other driver genomic alterations, such as those in EGFR, KRAS, or ALK, thus multiple genomic alterations are extremely rare. Herein, we report a case of a 42-year-old man diagnosed with lung adenocarcinoma positive for a SDC4-ROS1 fusion, who was treated with crizotinib followed by three cycles of chemotherapy...
October 3, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28967920/keap1-loss-promotes-kras-driven-lung-cancer-and-results-in-dependence-on-glutaminolysis
#19
Rodrigo Romero, Volkan I Sayin, Shawn M Davidson, Matthew R Bauer, Simranjit X Singh, Sarah E LeBoeuf, Triantafyllia R Karakousi, Donald C Ellis, Arjun Bhutkar, Francisco J Sánchez-Rivera, Lakshmipriya Subbaraj, Britney Martinez, Roderick T Bronson, Justin R Prigge, Edward E Schmidt, Craig J Thomas, Chandra Goparaju, Angela Davies, Igor Dolgalev, Adriana Heguy, Viola Allaj, John T Poirier, Andre L Moreira, Charles M Rudin, Harvey I Pass, Matthew G Vander Heiden, Tyler Jacks, Thales Papagiannakopoulos
Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function mutations in the KEAP1 gene encoding Kelch-like ECH-associated protein 1 (refs. 2, 3, 4), a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response...
October 2, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28966872/rapid-magnetic-isolation-of-extracellular-vesicles-via-lipid-based-nanoprobes
#20
Yuan Wan, Gong Cheng, Xin Liu, Si-Jie Hao, Merisa Nisic, Chuan-Dong Zhu, Yi-Qiu Xia, Wen-Qing Li, Zhi-Gang Wang, Wen-Long Zhang, Shawn J Rice, Aswathy Sebastian, Istvan Albert, Chandra P Belani, Si-Yang Zheng
Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. The pathophysiological roles and clinical value of EVs are under intense investigation, yet most studies are limited by technical challenges in the isolation of nanoscale EVs (nEVs). Here, we report a lipid nanoprobe that enables spontaneous labelling and magnetic enrichment of nEVs in 15 minutes, with isolation efficiency and cargo composition similar to what can be achieved by the much slower and bulkier method of ultracentrifugation...
2017: Nature biomedical engineering
keyword
keyword
19482
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"