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https://www.readbyqxmd.com/read/28214977/braf-mutated-colorectal-cancer-what-is-the-optimal-strategy-for-treatment
#1
REVIEW
Romain Cohen, Pascale Cervera, Magali Svrcek, Anna Pellat, Chantal Dreyer, Aimery de Gramont, Thierry André
The BRAF activating mutation, harbored by approximately 10% of colorectal cancers (CRC), confers dramatic prognosis to advanced diseases. In early-stage setting, the identification of the BRAF mutation does not impact the therapeutic decision. Yet, the BRAF mutation could be considered as a stratification factor in adjuvant trials, because of its prognostic impact after relapse. Moreover, both BRAF mutation and mismatch repair (MMR) statuses should be determined in all CRC to help identify sporadic tumors versus Lynch syndrome-related tumors...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28213007/effect-of-dasatinib-on-emt-mediated-mechanism-of-resistance-against-egfr-inhibitors-in-lung-cancer-cells
#2
Yuichi Sesumi, Kenichi Suda, Hiroshi Mizuuchi, Yoshihisa Kobayashi, Katsuaki Sato, Masato Chiba, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
OBJECTIVE: The epithelial to mesenchymal transition (EMT) is associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in certain non-small cell lung cancers that harbor EGFR mutations. Because no currently available drugs specifically kill cancer cells via EMT, novel treatment strategies that overcome or prevent EMT are needed. A recent report suggested that dasatinib (an ABL/Src kinase inhibitor) inhibits EMT induced by transforming growth factor (TGF)-beta in lung cancer cells (Wilson et al...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28213001/predictive-factors-for-egfr-tyrosine-kinase-inhibitor-retreatment-in-patients-with-egfr-mutated-non-small-cell-lung-cancer-a-multicenter-retrospective-sequence-study
#3
Gee-Chen Chang, Chien-Hua Tseng, Kuo-Hsuan Hsu, Chong-Jen Yu, Cheng-Ta Yang, Kun-Chieh Chen, Tsung-Ying Yang, Jeng-Sen Tseng, Chien-Ying Liu, Wei-Yu Liao, Te-Chun Hsia, Chih-Yen Tu, Meng-Chih Lin, Ying-Huang Tsai, Meng-Jer Hsieh, Wen-Shuo Wu, Yuh-Min Chen
BACKGROUND: Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. MATERIALS AND METHODS: This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR-TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212996/analysis-of-a-panel-of-druggable-gene-mutations-and-of-alk-and-pd-l1-expression-in-a-series-of-thymic-epithelial-tumors-tets
#4
Marcello Tiseo, Angela Damato, Lucia Longo, Fausto Barbieri, Federica Bertolini, Alessandro Stefani, Mario Migaldi, Letizia Gnetti, Roberta Camisa, Paola Bordi, Sebastiano Buti, Giulio Rossi
INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms with different prognosis lacking consistent molecular alterations possibly leading to targeted therapy. We collected a consecutive series of TETs aimed at investigating the mutational status of druggable genes (EGFR, c-KIT, KRAS, BRAF, PDGFR-alpha and -beta, HER2 and c-MET) and the expression of ALK and PD-L1. PATIENTS AND METHODS: One hundred twelve consecutive cases of TETs and relative clinico-pathologic features were collected...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212993/efficacy-according-to-blind-independent-central-review-post-hoc-analyses-from-the-phase-iii-randomized-multicenter-ipass-study-of-first-line-gefitinib-versus-carboplatin-paclitaxel-in-asian-patients-with-egfr-mutation-positive-advanced-nsclc
#5
Yi-Long Wu, Nagahiro Saijo, Sumitra Thongprasert, J C-H Yang, Baohui Han, Benjamin Margono, Busayamas Chewaskulyong, Patrapim Sunpaweravong, Yuichiro Ohe, Yukito Ichinose, Jin-Ji Yang, Tony S K Mok, Helen Young, Vincent Haddad, Yuri Rukazenkov, Masahiro Fukuoka
OBJECTIVE: The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212572/concurrent-gene-alterations-with-egfr-mutation-and-treatment-efficacy-of-egfr-tkis-in-chinese-patients-with-non-small-cell-lung-cancer
#6
Wentao Hu, Yahui Liu, Jian Chen
PURPOSE: We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment. METHODS: Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211502/bisphosphonates-enhance-antitumor-effect-of-egfr-tkis-in-patients-with-advanced-egfr-mutant-nsclc-and-bone-metastases
#7
Guowei Zhang, Ruirui Cheng, Zengli Zhang, Tao Jiang, Shengxiang Ren, Zhiyong Ma, Sha Zhao, Caicun Zhou, Jun Zhang
Whether bisphosphonates could enhance the effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with EGFR mutation and bone metastases (BM) remains unknown. EGFR mutation status were collected from 1560 patients with NSCLC and BM. 356 NSCLC patients with EGFR mutation and BM were identified. Among them, 91 patients received EGFR-TKIs alone and 105 patients received EGFR-TKIs plus bisphosphonates as first-line therapy. Comparing to TKIs alone, EGFR-TKIs plus bisphosphonates had a statistically significant longer progression-free survival (PFS: 11...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208660/splice-variants-of-the-rtk-family-their-role-in-tumour-progression-and-response-to-targeted-therapy
#8
REVIEW
Cherine Abou-Fayçal, Anne-Sophie Hatat, Sylvie Gazzeri, Beatrice Eymin
Receptor tyrosine kinases (RTKs) belong to a family of transmembrane receptors that display tyrosine kinase activity and trigger the activation of downstream signalling pathways mainly involved in cell proliferation and survival. RTK amplification or somatic mutations leading to their constitutive activation and oncogenic properties have been reported in various tumour types. Numerous RTK-targeted therapies have been developed to counteract this hyperactivation. Alternative splicing of pre-mRNA has recently emerged as an important contributor to cancer development and tumour maintenance...
February 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208047/targeted-therapy-for-chronic-respiratory-disease-a-new-paradigm
#9
Peter G Gibson, Matthew J Peters, Claire E Wainwright
Targeted therapy has emerged as a highly effective treatment approach for chronic respiratory diseases. Many of these conditions have dismal outcomes; however, targeted therapy shows great results for the subgroup who respond. This represents a new way to approach these conditions and offers great promise as a future treatment direction. In severe eosinophilic asthma, therapy that targets the interleukin-5 pathway with monoclonal antibodies leads to a 50% reduction in asthma exacerbations in previously refractory disease...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28207548/egfr-mutation-testing-in-blood-for-guiding-egfr-tyrosine-kinase-inhibitor-treatment-in-patients-with-nonsmall-cell-lung-cancer-a-protocol-for-systematic-review-and-meta-analysis
#10
Jin-Qiu Yuan, Yue-Lun Zhang, Hai-Tao Li, Chen Mao
BACKGROUND: Epidermal growth factor receptor (EGFR) mutation testing in tumor tissue is now a common practice in selecting non-small cell lung cancer (NSCLC) patients for EGFR tyrosine kinase inhibitor (TKI) treatment. However, tumor tissues are often absent or insufficient for the testing. Blood is a potential substitute providing a noninvasive, easily accessible and repeatedly measureable source of genotypic information. However which is the best blood EGFR mutation testing method remains unclear...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28205231/analysis-of-ctdna-to-predict-prognosis-and-monitor-treatment-responses-in-metastatic-pancreatic-cancer-patients
#11
He Cheng, Chen Liu, Jiahao Jiang, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Zhenzhen Zhang, Jin Xu, Liang Liu, Quanxing Ni, Xianjun Yu
Cell-free circulating tumor DNA (ctDNA) in plasma has been used as a potential noninvasive biomarker for various tumors. The current study was performed to evaluate the clinical implications of ctDNA detection in patients with metastatic pancreatic cancer. Firstly, we attempted to prospectively screen a panel of 60 genes in cell-free DNA (cfDNA) from ten metastatic pancreatic cancer patients via exome sequencing. Secondly, droplet digital PCR (ddPCR) was used to identify potential mutations in a cohort of 188 patients with metastatic pancreatic cancer...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28203297/therapeutic-approach-to-treating-patients-with-braf-mutant-lung-cancer-latest-evidence-and-clinical-implications
#12
REVIEW
Adrianus J de Langen, Egbert F Smit
Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28203260/yin-cold-or-yang-heat-syndrome-type-of-traditional-chinese-medicine-was-associated-with-the-epidermal-growth-factor-receptor-gene-status-in-non-small-cell-lung-cancer-patients-confirmation-of-a-tcm-concept
#13
Yan-Juan Zhu, Hai-Bo Zhang, Li-Rong Liu, Yi-Hong Liu, Fu-Li Zhang, Jian-Ping Bai, Yong Li, Yan-Chun Qu, Xin Qu, Xian Chen, Yan Li, Shu-Yi Luo, Ai-Hua Ou
Traditional Chinese Medicine (TCM) therapies should be tailored according to the different syndrome types. In order to identify the relationship between the TCM Yin-cold (YC) or Yang-heat (YH) syndrome types and the EGFR gene status, we prospectively studied 310 NSCLC patients. TCM YH or YC was diagnosed by three TCM experts. TCM symptoms and signs were entered into a binary cluster analysis. The relationships between the EGFR gene status, YH or YC syndrome types, and classification by cluster analysis were analyzed using the chi-square test and multivariate logistic regression...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28202526/radiation-resistance-in-kras-mutated-lung-cancer-is-enabled-by-stem-like-properties-mediated-by-an-osteopontin-egfr-pathway
#14
Meng Wang, Jing Han, Lynnette Marcar, Josh Black, Qi Liu, Xiangyong Li, Kshithija Nagulapalli, Lecia V Sequist, Raymond H Mak, Cyril H Benes, Theodore S Hong, Kristin Gurtner, Mechthild Krause, Michael Baumann, Jing X Kang, Johnathan Whetstine, Henning Willers
Lung cancers with activating KRAS mutations are characterized by treatment resistance and poor prognosis. In particular, the basis for their resistance to radiation therapy is poorly understood. Here we describe a radiation resistance phenotype conferred by a stem-like subpopulation characterized by mitosis-like condensed chromatin (MLCC), high CD133 expression, invasive potential, and tumor-initiating properties. Mechanistic investigations defined a pathway involving osteopontin and the EGFR in promoting this phenotype...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202511/amplification-of-egfr-wild-type-alleles-in-non-small-cell-lung-cancer-cells-confers-acquired-resistance-to-mutation-selective-egfr-tyrosine-kinase-inhibitors
#15
Shigenari Nukaga, Hiroyuki Yasuda, Katsuya Tsuchihara, Junko Hamamoto, Keita Masuzawa, Ichiro Kawada, Katsuhiko Naoki, Shingo Matsumoto, Sachiyo Mimaki, Shinnosuke Ikemura, Koichi Goto, Tomoko Betsuyaku, Kenzo Soejima
EGFR-mutated lung cancers account for a significant subgroup of non-small cell lung cancers overall. Third-generation EGFR tyrosine kinase inhibitors (TKI) are mutation-selective inhibitors with minimal effects on wild type EGFR. Acquired resistance develops to these agents, however, the mechanisms are as yet uncharacterized. In this study, we report that the Src-AKT pathway contributes to acquired resistance to these TKI. In addition, amplification of EGFR wild-type alleles but not mutant alleles was sufficient to confer acquired resistance...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#16
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199979/atm-mutations-and-e-cadherin-expression-define-sensitivity-to-egfr-targeted-therapy-in-colorectal-cancer
#17
Anna-Lena Geißler, Miriam Geißler, Daniel Kottmann, Lisa Lutz, Christiane D Fichter, Ralph Fritsch, Britta Weddeling, Frank Makowiec, Martin Werner, Silke Lassmann
EGFR-targeted therapy is a key treatment approach in patients with RAS wildtype metastatic colorectal cancers (CRC). Still, also RAS wildtype CRC may be resistant to EGFR-targeted therapy, with few predictive markers available for improved stratification of patients. Here, we investigated response of 7 CRC cell lines (Caco-2, DLD1, HCT116, HT29, LS174T, RKO, SW480) to Cetuximab and correlated this to NGS-based mutation profiles, EGFR promoter methylation and EGFR expression status as well as to E-cadherin expression...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198009/endoscopic-ultrasound-guided-fine-needle-aspirate-derived-preclinical-pancreatic-cancer-models-reveal-panitumumab-sensitivity-in-kras-wild-type-tumours
#18
William Berry, Elizabeth Algar, Beena Kumar, Christopher Desmond, Michael Swan, Brendan J Jenkins, Daniel Croagh
Pancreatic cancer (PC) is largely refractory to existing therapies used in unselected patient trials, thus emphasizing the pressing need for new approaches for patient selection in personalized medicine. KRAS mutations occur in 90% of PC patients and confer resistance to epidermal growth factor receptor (EGFR) inhibitors (e.g. panitumumab), suggesting that KRAS wild-type PC patients may benefit from targeted panitumumab therapy. Here we use tumour tissue procured by endoscopic ultrasound-guided fine-needle aspirate (EUS-FNA) to compare the in vivo sensitivity in patient derived xenografts (PDXs) of KRAS wild-type and mutant PC tumours to panitumumab, and to profile the molecular signature of these tumours in patients with metastatic or localized disease...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28198003/induction-of-cbl-dependent-epidermal-growth-factor-receptor-degradation-in-ling-zhi-8-suppressed-lung-cancer
#19
Tung-Yi Lin, Hsien-Yeh Hsu, Wei-Hsuan Sun, Tsung-Han Wu, Shu-Ming Tsao
Activating mutation of epidermal growth factor receptor (EGFR) is correlated with malignant lung tumor. In this study, we demonstrated that recombinant LZ-8 (rLZ-8), a medicinal mushroom Ganoderma lucidum protein, induced cell cycle arrest and apoptosis by downregulating the expression of wild-type and mutated EGFR and inhibiting EGFR downstream effectors, AKT and ERK1/2 in lung cancer cells. We showed that rLZ-8 effectively inhibited lung cancer progression and suppressed EGFR expression of lung tumor lesions in mouse model...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28197220/association-between-thyroid-cancer-and-epidermal-growth-factor-receptor-mutation-in-female-with-nonsmall-cell-lung-cancer
#20
Seo Yun Kim, Hye-Ryoun Kim, Cheol Hyeon Kim, Jae Soo Koh, Hee Jong Baek, Chang-Min Choi, Joon Seon Song, Jae Cheol Lee, Im Ii Na
BACKGROUND: The aim of this study was to investigate the association between epidermal growth factor receptor (EGFR) mutation and thyroid cancer in female patients with nonsmall-cell lung cancer (NSCLC). METHODS: In a retrospective study, we examined 835 female patients who were diagnosed with NSCLC and underwent an EGFR mutation test between June 2003 and August 2013. The associations of EGFR mutation with thyroid cancer and a family history of thyroid cancer were evaluated using logistic regression models...
January 2017: Annals of Thoracic Medicine
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