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https://www.readbyqxmd.com/read/29143497/detection-and-monitoring-of-driver-mutations-by-next-generation-sequencing-in-squamous-cell-lung-cancer-patient-and-possible-predictive-biomarker-of-third-generation-egfr-tyrosine-kinase-inhibitors
#1
Xiaoyan Shen, Jie Shen, Hang Zhang, Yuxin Cheng, Yang Yang, Jiahui Gao, Yu Zhang, Rutian Li, Baorui Liu, Lifeng Wang
Driver mutation detection and the development of targeted drugs have significantly improved survival of advanced lung adenocarcinoma patients with driver mutations. However, we still lack understanding of druggable mutations in patients with advanced squamous cell lung cancer (SQCLC). Less than 10% of SQCLC patients have EGFR gene mutations, thus we have limited knowledge of biological molecular changes with first generation EGFR-tyrosine kinase inhibitor (TKI) resistance. We report a case of an SQCLC patient treated with first-line platinum-doublet chemotherapy...
November 16, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29138221/immature-cml-cells-implement-a-bmp-autocrine-loop-to-escape-tki-treatment
#2
Elodie Grockowiak, Bastien Laperrousaz, Sandrine Jeanpierre, Thibault Voeltzel, Boris Guyot, Stéphanie Gobert, Franck E Nicolini, Véronique Maguer-Satta
The BCR-ABL specific Tyrosine Kinase Inhibitors (TKI) changed the outcome of Chronic Myeloid Leukemia (CML), turning a life-threatening disease into a chronic illness. However, TKI are not yet curative, since most patients retain leukemic stem cells (LSC) and their progenitors in bone marrow and relapse following treatment cessation. At diagnosis, deregulations of the Bone Morphogenetic Proteins (BMP) pathway are involved in LSC and progenitors expansion. Here, we report that BMP pathway alterations persist in TKI-resistant patients...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29137227/re-balance-of-memory-t-cell-subsets-in-peripheral-blood-from-patients-with-cml-after-tki-treatment
#3
Danlin Yao, Ling Xu, Jiaxiong Tan, Yikai Zhang, Shuai Lu, Mingde Li, Sichun Lu, Lijian Yang, Shaohua Chen, Jie Chen, Jing Lai, Yuhong Lu, Xiuli Wu, Xianfeng Zha, Yangqiu Li
T cell immune surveillance is considered an important host protection process for inhibiting carcinogenesis. The full capacity of T cell immune surveillance is dependent on T cell homeostasis, particularly for central memory T (TCM) cells and stem cell memory T (TSCM) cells. In this study, distribution of T cell subsets in peripheral blood from 12 patients with chronic myeloid leukemia (CML) and 12 cases with CML in complete remission (CR) was analyzed using a multicolor flow cytometer, and 16 samples from healthy individuals (HIs) served as control...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133777/acute-lymphoblastic-leukemia-patient-with-variant-atf7ip-pdgfrb-fusion-and-favorable-response-to-tyrosine-kinase-inhibitor-treatment-a-case-report
#4
Ge Zhang, Yanle Zhang, Jianrong Wu, Yan Chen, Zhigui Ma
BACKGROUND Chromosomal translocations involving the PDGFRB gene have been reported in a broad spectrum of hematological malignancies. An ATF7IP/PDGFRB fusion was recently identified in a Philadelphia chromosome-like (Ph-like) B-progenitor acute lymphoblastic leukemia (B-ALL) patient. Here we report on a special case of a Ph-like ALL patient who had a variant ATF7IP/PDGFRB fusion. CASE REPORT In this case, a variant fusion was created between ATF7IP exon 9 (instead of exon 13) and PDGFRB exon 11, resulting in the loss of 411 nucleotides and 137 amino acids in the ATF7IP/PDGFRB fusion cDNA and its encoded chimeric protein, respectively...
November 14, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29128554/immunomodulatory-effects-of-tyrosine-kinase-inhibitors-tkis-in-vitro-and-in-vivo-study
#5
Elena Marinelli Busilacchi, Andrea Costantini, Nadia Viola, Benedetta Costantini, Jacopo Olivieri, Luca Butini, Giorgia Mancini, Ilaria Scortechini, Martina Chiarucci, Monica Poiani, Antonella Poloni, Pietro Leoni, Attilio Olivieri
Pathogenesis of chronic Graft Versus Host Disease (cGVHD) is incompletely defined, involving donor-derived CD4 and CD8-positive T lymphocytes, as well as B cells. Standard treatment is lacking for steroid dependent/refractory cases; potential usefulness of tyrosine kinase inhibitors (TKIs) has been suggested, based on their potent anti-fibrotic effect. However, TKI seems to have pleiotropic activity. We sought to evaluate the in vitro and in vivo impact of different TKIs on lymphocyte phenotype and function...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29123416/frequency-and-clinical-relevance-of-egfr-mutations-and-eml4-alk-translocations-in-octogenarians-with-non-small-cell-lung-cancer
#6
Amanda Tufman, Kathrin Kahnert, Thomas Duell, Diego Kauffmann-Guerrero, Katrin Milger, Christian Schneider, Julia Stump, Zulfiya Syunyaeva, Rudolf Maria Huber, Simone Reu
Background: Tyrosine kinase inhibitors (TKIs) have improved response rates in some patients with non-small cell lung cancer (NSCLC), and testing for EGFR mutation and ALK translocation is recommended for all patients with advanced lung adenocarcinoma. The frequency of driver mutations in elderly and very elderly patients has not been described. Patients and methods: We reviewed EGFR and ALK in patients over the age of 70 years diagnosed and treated at our center in 2015 (subgroups: 70-74, 75-79 and >80 years)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29123415/impact-of-hypertrophic-pulmonary-osteoarthropathy-on-patients-with-lung-cancer
#7
Yu-Hung Fang, Chien-Chin Hsu, Meng-Jer Hsieh, Ming-Szu Hung, Ying-Huang Tsai, Yu-Ching Lin
Purpose: Hypertrophic pulmonary osteoarthropathy (HPOA) is a rare disease that most commonly occurs secondary to lung cancer. However, the clinical significance of HPOA remains unclear. The aim of this study was to evaluate the impact of HPOA on patients with lung cancer in Taiwan. Patients and methods: Data regarding lung cancer patients who demonstrated findings of HPOA on bone scintigraphy between 2010 and 2016 were retrospectively analyzed. Pathological confirmation of cases was conducted at Chiayi and Kaohsiung Chang Gang Memorial Hospital...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29121501/does-c-met-remain-a-rational-target-for-therapy-in-patients-with-egfr-tki-resistant-non-small-cell-lung-cancer
#8
REVIEW
Yi-Long Wu, Ross Andrew Soo, Giuseppe Locatelli, Uz Stammberger, Giorgio Scagliotti, Keunchil Park
Non-small cell lung cancer (NSCLC) inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. In 5-20% of cases, this can be attributed to aberrant c-Met activity, providing a clear rationale for the use of c-Met inhibitors in these patients. EGFR TKI-resistant tumors often remain sensitive to EGFR signaling, such that c-Met inhibitors are likely to be most effective when combined with continued EGFR TKI therapy. The phase III trials of the c-Met inhibitors onartuzumab and tivantinib, which failed to demonstrate significant benefit in patients with NSCLC but excluded patients with EGFR TKI-resistant disease, do not allow c-Met to be dismissed as a rational target in EGFR TKI-resistant NSCLC...
October 25, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29121435/altered-intracellular-signaling-by-imatinib-increases-the-anti-cancer-effects-of-tyrosine-kinase-inhibitors-in-cml-cells
#9
Takuya Hirao, Masashi Yamaguchi, Megumi Kikuya, Hiroji Chibana, Kousei Ito, Shigeki Aoki
Tyrosine kinase inhibitors (TKIs), including imatinib (IM), improve the outcome of chronic myelogenous leukemia (CML) therapy. However, TKI treatment is long-term and can induce resistance to TKIs, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome-positive CML cell line, and its subsequent sensitivity to anti-cancer agents. Contrary to our expectations, we found that continuous IM exposure increased sensitivity to TKIs...
November 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/29120911/immunotherapy-for-kidney-cancer-status-quo-and-the-future
#10
Jens Bedke, Viktoria Stühler, Arnulf Stenzl, Bernhard Brehmer
PURPOSE OF REVIEW: The treatment landscape in advanced and metastatic renal cell carcinoma (RCC) is moving from the inhibition of tyrosine kinases (TKI) and the mammalian target of rapamycin (mTOR) inhibitors to specific immunooncology agents like immune checkpoint inhibitors (ICI). The review focus on the recent immunooncology developments and available trial results within the last 12 months. RECENT FINDINGS: ICI as monotherapy (nivolumab) or immunooncology and immunooncology combinations (nivolumab and ipilimumab) demonstrated positive results on prolonged overall survival in phase III trials...
November 7, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/29120087/histological-evolution-from-primary-lung-adenocarcinoma-harboring-egfr-mutation-to-high-grade-neuroendocrine-carcinoma
#11
Jikai Zhao, Jinchen Shao, Ruiying Zhao, Rong Li, Keke Yu, Lei Zhu, Jie Zhang
BACKGROUND: Although patients with EGFR mutated lung adenocarcinoma benefit greatly from tyrosine kinase inhibitors (TKIs), they inevitably develop acquired resistance after an average of 10-14 months of continuous treatment. METHODS: We retrospectively analyzed the clinical and histopathological data of eight patients with primary lung adenocarcinoma harboring EGFR mutations that transformed into high-grade neuroendocrine carcinoma after TKI therapy. Morphology scanning for neuroendocrine differentiation and immunohistochemistry for neuroendocrine markers CD56, chromogranin, and synaptophysin were performed on primary adenocarcinoma tissues and repeated biopsies...
November 9, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29119148/brigatinib-for-the-treatment-of-alk-positive-advanced-non-small-cell-lung-cancer-patients
#12
A Passaro, A Prelaj, A Pochesci, G Spitaleri, G Rossi, E Del Signore, C Catania, F de Marinis
Brigatinib (AP-26113, Alunbrig) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that is highly active in non-small cell lung cancer (NSCLC) harboring ALK translocation. Brigatinib was found to be very active against different ALK resistance mutations that mediate acquired resistance biology processes, particularly G1269A ALK C1156Y, I1171S/T, V1180L and others. Different clinical trials evaluated the activity of brigatinib in crizotinib-resistant patients, confirming high activity with durable response not only in parenchymal disease, but also in intracranial disease...
August 2017: Drugs of Today
https://www.readbyqxmd.com/read/29119113/increased-egfr-phosphorylation-correlates-with-higher-programmed-death-ligand-1-expression-analysis-of-tki-resistant-lung-cancer-cell-lines
#13
Kenichi Suda, Leslie Rozeboom, Koh Furugaki, Hui Yu, Mary Ann C Melnick, Kim Ellison, Christopher J Rivard, Katerina Politi, Tetsuya Mitsudomi, Fred R Hirsch
Despite the recent development of immunotherapies that target programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) treatment, these therapies are less effective in NSCLC patients with epidermal growth factor receptor (EGFR) mutations. However, the molecular mechanisms underlying this lower efficacy of immunotherapies in EGFR mutant lung cancers are still unclear. In this study, we analyzed PD-L1 protein expression in lung cancer cell lines with EGFR mutations prior to and after acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29118262/stress-hormones-promote-egfr-inhibitor-resistance-in-nsclc-implications-for-combinations-with-%C3%AE-blockers
#14
Monique B Nilsson, Huiying Sun, Lixia Diao, Pan Tong, Diane Liu, Lerong Li, Youhong Fan, Alissa Poteete, Seung-Oe Lim, Kathryn Howells, Vincent Haddad, Daniel Gomez, Hai Tran, Guillermo Armaiz Pena, Lecia V Sequist, James C Yang, Jing Wang, Edward S Kim, Roy Herbst, J Jack Lee, Waun Ki Hong, Ignacio Wistuba, Mien-Chie Hung, Anil K Sood, John V Heymach
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance mediated by T790M-independent mechanisms remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). We identified a targetable mechanism of EGFR inhibitor resistance whereby stress hormones activate β2-adrenergic receptors (β2-ARs) on NSCLC cells, which cooperatively signal with mutant EGFR, resulting in the inactivation of the tumor suppressor, liver kinase B1 (LKB1), and subsequently induce interleukin-6 (IL-6) expression...
November 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29115640/off%C3%A2-target-effect-of-imatinib-and-nilotinib-on-human-vitamin-d3-metabolism
#15
Lysann Kroschwald, Meinolf Suttorp, Josephine Tabea Tauer, Nick Zimmermann, Claudia Günther, Andrea Bauer
Prolonged treatment with tyrosine kinase inhibitors (TKI) including imatinib (IMA) or nilotinib (NIL), induces severe disturbances of bone metabolism in patients with chronic myeloid leukaemia. As vitamin D3 (VD3) is involved in the complex cycle of bone remodelling, the present study investigated in vitro, the influence of IMA and NIL on VD3 metabolism i) in HaCaT cells and ii) in cultured outer root sheath keratinocytes (ORS‑KC) from hair follicles of IMA treated children. Cells were incubated in the presence of IMA or NIL...
November 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111173/epidermal-growth-factor-receptor-mutation-predicts-favorable-outcomes-in-non-small-cell-lung-cancer-patients-with-brain-metastases-treated-with-stereotactic-radiosurgery
#16
Wen-Chi Yang, Furen Xiao, Jin-Yuan Shih, Chao-Chi Ho, Ya-Fang Chen, Ham-Min Tseng, Kuan-Yu Chen, Wei-Yu Liao, Chong-Jen Yu, James Chih-Hsin Yang, Sung-Hsin Kuo, Jason Chia-Hsien Cheng, Pan-Chyr Yang, Feng-Ming Hsu
PURPOSE: The impact of epidermal growth factor receptor (EGFR) mutations on radiotherapy for brain metastases (BM) is undetermined. We evaluated the effects of EGFR mutation status on responses and outcomes in non-small cell lung cancer (NSCLC) patients with BM, treated with upfront or salvage stereotactic radiosurgery (SRS). METHODS AND MATERIALS: From 2008 to 2015, 147 eligible NSCLC patients with 300 lesions were retrospectively analyzed. Patterns of tyrosine kinase inhibitor (TKI) therapy were recorded...
October 27, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29110841/heterogeneous-resistance-mechanisms-in-an-egfr-exon-19-mutated-non-small-cell-lung-cancer-patient-treated-with-erlotinib-persistent-fgfr3-mutation-localized-transformation-to-egfr-mutated-sclc-and-acquired-t790m-egfr-mutation
#17
Eric Santoni-Rugiu, Morten Grauslund, Linea C Melchior, Junia C Costa, Jens B Sørensen, Edyta M Urbanska
Patients with epidermal growth factor receptor (EGFR) gene-mutated non-small cell lung cancer (NSCLC) obtain substantial clinical benefit from EGFR tyrosine-kinase inhibitors (TKIs), but will ultimately develop TKI-resistance resulting in median progression-free survival of 9-15 months during first-line TKI-therapy. However, type and timing of TKI-resistance cannot be predicted and several mechanisms may simultaneously/subsequently occur during TKI-treatment. In this respect, we present a 49 year-old Caucasian male ex-smoker with metastatic pulmonary adenocarcinoma (ADC) that concomitantly harbored an EGFR exon 19-mutation (p...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110836/next-generation-sequencing-reveals-novel-resistance-mechanisms-and-molecular-heterogeneity-in-egfr-mutant-non-small-cell-lung-cancer-with-acquired-resistance-to-egfr-tkis
#18
Choong-Kun Lee, Sora Kim, Jae Seok Lee, Jeong Eun Lee, Sung-Moo Kim, In Seok Yang, Hye Ryun Kim, Jeong Ho Lee, Sangwoo Kim, Byoung Chul Cho
OBJECTIVES: Despite initial responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant non-small cell lung cancer, patients invariably develop acquired resistance. In this study, we performed next-generation sequencing in pre- and post-EGFR-TKI tumor samples to identify novel resistance mechanisms to EGFR-TKIs. MATERIAL AND METHODS: We collected tumor tissues before EGFR-TKI treatment and after progression from 19 NSCLC patients to analyze genomic alterations in 409 cancer related genes...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29110716/postoperative-survival-of-egfr-tki-targeted-therapy-in-non-small-cell-lung-cancer-patients-with-egfr-19-or-21-mutations-a-retrospective-study
#19
Wenjing Yang, Yibo Gao, Xuelian Li, Jing Zhang, Tiejun Liu, Xiaoli Feng, Hao Pan, Xiaofan Yang, Shuanghua Xie, Xiaoshuang Feng, Zhangyan Lv, Yonggang Wang, Zhaoli Chen, Jie He
BACKGROUND: The aim of this retrospective study is to identify epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer patients and to compare the long-term postoperative outcomes in different EGFR-TKI-targeted therapy effects between the different EGFR mutation groups. METHODS: A total of 2094 postoperative non-small cell lung cancer (NSCLC) patients with EGFR gene detection were collected in the Department of Pathology in the Cancer Hospital Chinese Academy of Medical Sciences from January 2003 to January 2014...
November 6, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29110548/new-targets-and-therapies-for-gastrointestinal-stromal-tumors
#20
Agnieszka Wozniak, Yemarshet K Gebreyohannes, Maria Debiec-Rychter, Patrick Schöffski
The majority of gastrointestinal stromal tumors (GIST) are driven by an abnormal receptor tyrosine kinase (RTK) signaling, occurring mainly due to somatic mutations in KIT or platelet derived growth factor receptor alpha (PDGFRA). Although the introduction of tyrosine kinase inhibitors (TKIs) has revolutionized therapy for GIST patients, with time the vast majority of them develop TKI resistance. Advances in understanding the molecular background of GIST resistance allows for the identification of new targets and the development of novel strategies to overcome or delay its occurrence...
November 7, 2017: Expert Review of Anticancer Therapy
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