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https://www.readbyqxmd.com/read/28548967/detection-of-activating-and-acquired-resistant-mutation-in-plasma-from-egfr-mutated-nsclc-patients-by-peptide-nucleic-acid-pna-clamping-assisted-fluorescence-melting-curve-analysis
#1
Chang Gon Kim, Hyo Sup Shim, Min Hee Hong, Yoon Jin Cha, Su Jin Heo, Hyung Soon Park, Jee Hung Kim, Jin Gu Lee, Chang Young Lee, Byoung Chul Cho, Hye Ryun Kim
This study was designed to prospectively examine whether peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper™) is feasible for the detection of activating and acquired resistant epidermal growth factor receptor (EGFR) mutation in plasma. Patients with non-small cell lung cancer harboring activating EGFR mutations who were scheduled to undergo EGFR-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled between September 2011 and March 2015. A total of 102 patients with EGFR-mutated lung cancer were enrolled, 53 had available plasma samples at disease progression, and 28 underwent serial plasma sampling during EGFR-TKI treatment...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28543934/clinical-impact-of-pre-transplant-use-of-multiple-tyrosine-kinase-inhibitors-on-the-outcome-of-allo-hsct-for-cml
#2
Takeshi Kondo, Tokiko Nagamura-Inoue, Arinobu Tojo, Fumitaka Nagamura, Naoyuki Uchida, Hirohisa Nakamae, Takahiro Fukuda, Takehiko Mori, Shingo Yano, Mineo Kurokawa, Hironori Ueno, Heiwa Kanamori, Hisako Hashimoto, Makoto Onizuka, Minoko Takanashi, Tatsuo Ichinohe, Yoshiko Atsuta, Kazuteru Ohashi
Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with chronic myelogenous leukemia in the chronic phase (CML-CP), and outcomes of TKI treatment for patients with CML-CP have been excellent. Since multiple TKIs are currently available, second-line or third-line TKI therapy is considered for patients who are intolerant of or resistant to the previous TKI treatment. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered only for patients with disease progression or for patients after treatment failure with multiple TKIs...
May 20, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28537914/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#3
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533480/deregulated-expression-of-mir-29a-3p-mir-494-3p-and-mir-660-5p-affects-sensitivity-to-tyrosine-kinase-inhibitors-in-cml-leukemic-stem-cells
#4
Simona Salati, Valentina Salvestrini, Chiara Carretta, Elena Genovese, Sebastiano Rontauroli, Roberta Zini, Chiara Rossi, Samantha Ruberti, Elisa Bianchi, Greta Barbieri, Antonio Curti, Fausto Castagnetti, Gabriele Gugliotta, Gianantonio Rosti, Micaela Bergamaschi, Agostino Tafuri, Enrico Tagliafico, Roberto Lemoli, Rossella Manfredini
The development of Imatinib mesylate (IM), which targets the oncogenic BCR-ABL fusion protein, has greatly improved the outcome of Chronic Myeloid Leukemia (CML) patients. However, BCR-ABL-positive progenitors can be detected in CML patients in complete cytogenetic response. Several evidence suggests that CML stem cells are intrinsically resistant to Tyrosine Kinase Inhibitors (TKI), and therefore they represent the most likely candidate responsible for disease relapse.In this work, we investigated the microRNA (miRNA) expression profile of different subpopulations of CML Leukemic Stem Cells (LSCs): Lin-CD34+CD38- and Lin-CD34-CD38- cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529628/cross-platform-comparison-of-four-leading-technologies-for-detecting-egfr-mutations-in-circulating-tumor-dna-from-non-small-cell-lung-carcinoma-patient-plasma
#5
Ting Xu, Xiaozheng Kang, Xiaofang You, Liang Dai, Dequan Tian, Wanpu Yan, Yongbo Yang, Hongchao Xiong, Zhen Liang, Grace Q Zhao, Shengrong Lin, Ke-Neng Chen, Guobing Xu
Analysis of circulating tumor DNA (ctDNA) is emerging as a powerful tool for guiding targeted therapy and monitoring tumor evolution in patients with non-small cell lung cancer (NSCLC), especially when representative tissue biopsies are not available. Here, we have compared the ability of four leading technology platforms to detect epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, T790M and G719X) in ctDNA from NSCLC patients. Two amplification refractory mutation systems (cobas-ARMS and ADx-ARMS), a droplet digital polymerase chain reaction (ddPCR) and a next-generation sequencing (Firefly NGS) platform were included in the comparison...
2017: Theranostics
https://www.readbyqxmd.com/read/28525890/a-novel-egfr-tki-inhibitor-camp-h3bo3%C3%A2-complex-combined-with-thermal-therapy-is-a-promising-strategy-to-improve-lung-cancer-treatment-outcomes
#6
Yongpeng Tong, Chunliu Huang, Junfang Zhang
PURPOSE: Although EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) induce favorable responses as first-line non-small cell lung cancer treatments, drug resistance remains a serious problem. Meanwhile, thermal therapy also shows promise as a cancer therapy strategy. Here we combine a novel EGFR-TKI treatment with thermal therapy to improve lung cancer treatment outcomes. RESULTS: The results suggest that the cAMP-H3BO3 complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest in vitro...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521430/reduced-expression-levels-of-pten-are-associated-with-decreased-sensitivity-of-hcc827-cells-to-icotinib
#7
Yang Zhai, Yanjun Zhang, Kejun Nan, Xuan Liang
The clinical resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been linked to EGFR T790M resistance mutations or MET amplifications. Additional mechanisms underlying EGFR-TKI drug resistance remain unclear. The present study demonstrated that icotinib significantly inhibited the proliferation and increased the apoptosis rate of HCC827 cells; the cellular mRNA and protein expression levels of phosphatase and tensin homolog (PTEN) were also significantly downregulated...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521421/an-unusual-translocation-t-1-11-q21-q23-in-a-case-of-chronic-myeloid-leukemia-with-a-cryptic-philadelphia-chromosome
#8
Leandro Germán Gutiérrez, María Fernanda Noriega, Alejandro Laudicina, Mariana Quatrin, Raquel María Bengió, Irene Larripa
Chronic myeloid leukemia (CML) is characterized by the translocation t(9;22)(q34;q11) [Philadelphia (Ph) chromosome). Although not frequently occurring, additional chromosome abnormalities (ACAs) can be detected at diagnosis and a number have been associated with an adverse cytogenetic and molecular outcome. The present study reports a case of CML presenting with the translocation t(1;11)(q21;q23) and a cryptic Ph chromosome. The presence of ACAs could generate greater genetic instability, promoting the emergence of further alterations...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520590/role-of-tyrosine-kinase-inhibitors-in-the-treatment-of-pituitary-tumours-from-bench-to-bedside
#9
Anat Ben-Shlomo, Odelia Cooper
PURPOSE OF REVIEW: Treatment of aggressive pituitary tumours often yields suboptimal control of the tumour and confers significant morbidity. Lactotroph and corticotroph-derived tumours express ErbB receptors and ligands, and mutations in ubiquitin-specific protease 8 (USP8), which alters epidermal growth factor receptor (EGFR) degradation, have been implicated in Cushing disease pathogenesis. EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a potential new therapeutic approach for patients with aggressive prolactinomas and Cushing disease...
May 17, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28515374/polyphyllin-i-overcomes-emt-associated%C3%A2-resistance%C3%A2-to-erlotinib-in-lung-cancer-cells-via-il-6-stat3-pathway-inhibition
#10
Wei Lou, Yan Chen, Ke-Ying Zhu, Huizi Deng, Tianhao Wu, Jun Wang
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the most important limiting factor for treatment efficiency in EGFR-mutant non-small cell lung cancer (NSCLC). Much work has linked the epithelial-mesenchymal transition (EMT) to the emergence of drug resistance, consequently, ongoing research has been focused on exploring the therapeutic options to reverse EMT for delaying or preventing drug resistance. Polyphyllin I (PPI) is a natural compound isolated from Paris polyphylla rhizomes and displayed anti-cancer properties...
May 18, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28503070/tyrosine-kinase-inhibitor-combination-therapy-in-first-line-treatment-of-non-small-cell-lung-cancer-systematic-review-and-network-meta-analysis
#11
Sarah Batson, Stephen A Mitchell, Ricarda Windisch, Elisabetta Damonte, Veronica C Munk, Noemi Reguart
INTRODUCTION: The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients develop resistance, with the result that median progression-free survival (PFS) iŝ12 months. Combining EGFR-TKIs with other agents, such as bevacizumab, is a promising approach to prolonging remission. This systematic review and network meta-analysis (NMA) were undertaken to assess available evidence regarding the benefits of first-line combination therapy involving EGFR-TKIs in patients with advanced NSCLC...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28501913/chronic-myeloid-leukemia-immunobiology-and-novel-immunotherapeutic-approaches
#12
Emilie Cayssials, Francois Guilhot
Imatinib has revolutionized the treatment and prognosis of chronic myeloid leukemia (CML) with survival rates now approaching those of the age-matched healthy population. To be able to discontinue tyrosine kinase inhibitor (TKI) treatment, it is necessary to develop complementary therapies to target minimal residual disease. Recent findings by a number of investigators in both CML mouse models and CML patients offer evidence that many factors in the leukemic microenvironment can collectively contribute to immune escape, including expansion of myeloid-derived suppressor cells, programmed death-1/programmed death-1 ligand interactions resulting in T-cell impairment, expression of soluble suppressive factors such as soluble CD25, and down-regulation of MHC molecules by CML cells...
May 13, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28499791/the-role-of-radiotherapy-in-epidermal-growth-factor-receptor-mutation-positive-patients-with-oligoprogression-a-matched-cohort-analysis
#13
O S H Chan, V H F Lee, T S K Mok, F Mo, A T Y Chang, R M W Yeung
AIMS: Almost all patients with epidermal growth factor receptor (EGFR) mutations will develop resistance to first-line EGFR tyrosine kinase inhibitors (TKIs). The management of oligoprogression on EGFR TKI is controversial. Irradiating progressing tumours may potentially eradicate the resistant clone and allow continuation of EGFR TKI, but the clinical data remain sparse. We aimed to assess the effect of radiotherapy on survival outcomes in patients with oligoprogression in a matched-cohort study...
May 9, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28498782/clonal-history-and-genetic-predictors-of-transformation-into-small-cell-carcinomas-from-lung-adenocarcinomas
#14
June-Koo Lee, Junehawk Lee, Sehui Kim, Soyeon Kim, Jeonghwan Youk, Seongyeol Park, Yohan An, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo, Young Tae Kim, Jin-Soo Kim, Se Hyun Kim, Jong Seok Lee, Se-Hoon Lee, Keunchil Park, Ja-Lok Ku, Yoon Kyung Jeon, Doo Hyun Chung, Peter J Park, Joon Kim, Tae Min Kim, Young Seok Ju
Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied for nine tumors acquired at various time points from four patients to reconstruct their clonal evolutionary history and to detect genetic predictors for small-cell transformation...
May 12, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28498399/dual-inhibition-of-igf1r-and-er-enhances-response-to-trastuzumab-in-her2-positive-breast-cancer-cells
#15
Martina S J McDermott, Alexandra Canonici, Laura Ivers, Brigid C Browne, Stephen F Madden, Neil A O'Brien, John Crown, Norma O'Donovan
Although HER2 targeted therapies have improved prognosis for HER2 positive breast cancer, HER2 positive cancers which co-express ER have poorer response rates to standard HER2 targeted therapies, combined with chemotherapy, than HER2 positive/ER negative breast cancer. Administration of hormone therapy concurrently with chemotherapy and HER2 targeted therapy is generally not recommended. Using publically available gene expression datasets we found that high expression of IGF1R is associated with shorter disease-free survival in patients whose tumors are ER positive and HER2 positive...
April 26, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28490925/management-of-egfr-mutated-non-small-cell-lung-cancer-practical-implications-from-a-clinical-and-pathology-perspective
#16
REVIEW
M Cabanero, R Sangha, B S Sheffield, M Sukhai, M Pakkal, S Kamel-Reid, A Karsan, D Ionescu, R A Juergens, C Butts, M S Tsao
Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc...
April 2017: Current Oncology
https://www.readbyqxmd.com/read/28490886/apatinib-to-combat-egfr-tki-resistance-in-an-advanced-non-small-cell-lung-cancer-patient-with-unknown-egfr-status-a-case-report
#17
Yanmei Peng, Huijuan Cui, Zhe Liu, Daiwei Liu, Fan Liu, Yazhong Song, Hua Duan, Yuqin Qiu, Qiang Li
Lung adenocarcinoma is the most common pathological pattern of lung cancer. During the past decades, a number of targeted agents have been explored to treat advanced lung adenocarcinoma. In the present clinical practice, antagonists of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF)-directed therapies are widely used. In the former category, the agent erlotinib (tyrosine kinase inhibitor) has shown obvious advantages over cytotoxic therapy. Anti-VEGF therapy bevacizumab used for lung adenocarcinoma was recommended in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as first-line therapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28490572/heterogeneous-resistance-to-quizartinib-in-acute-myeloid-leukemia-aml-revealed-by-single-cell-analysis
#18
Catherine C Smith, Amy Paguirigan, Grace R Jeschke, Kimberly C Lin, Evan Massi, Theodore Tarver, Chen-Shan Chin, Saurabh Asthana, Adam Olshen, Kevin J Travers, Susana Wang, Mark J Levis, Alexander E Perl, Jerald P Radich, Neil P Shah
Genomic studies have revealed significant branching heterogeneity in cancer. Studies of resistance to tyrosine kinase inhibitor (TKI) therapy have not fully reflected this heterogeneity as resistance in individual patients has been ascribed to largely mutually exclusive "on-target" or "off-target" mechanisms in which tumors either retain dependency on the target oncogene or subvert it through a parallel pathway. Using targeted sequencing from single cells and colonies from patient samples, we demonstrate tremendous clonal diversity in the majority of acute myeloid leukemia (AML) patients with activating FLT3 internal tandem duplication (ITD) mutations at the time of acquired resistance to the FLT3 inhibitor quizartinib...
May 10, 2017: Blood
https://www.readbyqxmd.com/read/28486985/the-salvage-therapy-in-lung-adenocarcinoma-initially-harbored-susceptible-egfr-mutation-and-acquired-resistance-occurred-to-the-first-line-gefitinib-and-second-line-cytotoxic-chemotherapy
#19
Chih-Jen Yang, Jen-Yu Hung, Ming-Ju Tsai, Kuan-Li Wu, Ta-Chih Liu, Shah-Hwa Chou, Jui-Ying Lee, Jui-Sheng Hsu, Ming-Shyan Huang, Inn-Wen Chong
BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib can provide better efficacy and prolonged progression free survival (PFS) than cytotoxic chemotherapy for metastatic lung non-squamous cell carcinoma harboring susceptible EGFR mutations when used as first-line therapy. Cytotoxic chemotherapy is regarded as being the standard therapy to overcome acquired resistance to an initial EGFR TKI. However, there is currently no consensus on how best to treat patients who develop resistance to both an initial EGFR TKI and chemotherapy...
May 10, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28484277/tyrosine-kinase-inhibitors-of-ripk2-attenuate-bacterial-cell-wall-mediated-lipolysis-inflammation-and-dysglycemia
#20
Brittany M Duggan, Kevin P Foley, Brandyn D Henriksbo, Joseph F Cavallari, Akhilesh K Tamrakar, Jonathan D Schertzer
Inflammation underpins aspects of insulin resistance and dysglycemia. Microbiota-derived cell wall components such as muropeptides or endotoxin can trigger changes in host immunity and metabolism. Specific peptidoglycan motifs promote metabolic tissue inflammation, lipolysis and insulin resistance via Nucleotide-binding oligomerization domain-containing protein 1 (Nod1). Receptor-interacting serine/threonine-protein kinase 2 (Ripk2) mediates Nod1-induced immunity, but the role of Ripk2 in metabolism is ill-defined...
May 8, 2017: Scientific Reports
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