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https://www.readbyqxmd.com/read/27931835/management-of-patients-with-recurrent-advanced-cervical-cancer-beyond-first-line-platinum-regimens-where-do-we-stand-a-literature-review
#1
REVIEW
Stergios Boussios, Esmeralda Seraj, George Zarkavelis, Dimitrios Petrakis, Aristomenes Kollas, Aikaterini Kafantari, Abraam Assi, Konstantina Tatsi, Nicholas Pavlidis, George Pentheroudakis
BACKGROUND: Cervical cancer is the fourth most common cancer affecting women worldwide. Despite advances in screening and human papillomavirus (HPV) vaccination, a significant number of women present with or develop advanced disease. Palliative platinum-based chemotherapy (CT) is the standard first-line treatment for metastatic/recurrent cervical cancer. The prognosis remains poor and effective second line options are urgently needed. METHODS: We searched the English-language medical literature as well as relevant guideline databases, published from January 1981 to December 2015 and identified publications related to cervical cancer and its therapies...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27931141/modulation-of-leukotriene-signaling-inhibiting-cell-growth-in-chronic-myeloid-leukemia
#2
Elham Yektaei-Karin, Ana Zovko, Anders Nilsson, Barbro Näsman-Glaser, Lena Kanter, Olof Rådmark, Jonas Wallvik, Marja Ekblom, Monika Dolinska, Hong Qian, Leif Stenke
Although tyrosine kinase inhibitors (TKIs) have dramatically improved clinical outcome in chronic myeloid leukemia (CML), cure rarely occurs. This may be due to BCR-ABL-independent, aberrant signaling pathways, one of which leads to leukotriene (LT) formation. Well-recognized as inflammatory mediators, LT can also affect oncogenic mechanisms of several tumors. We have previously discovered elevated LT-synthesis and up-regulated cysteinyl-LT-inducing enzyme in CML. Here we report on dose-dependent inhibition of CML cell growth exerted by specific blockers of LT-signaling...
December 8, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27930974/mir-200c-enhances-sensitivity-of-drug-resistant-non-small-cell-lung-cancer-to-gefitinib-by-suppression-of-pi3k-akt-signaling-pathway-and-inhibites-cell-migration-via-targeting-zeb1
#3
Guohua Zhou, Fangli Zhang, Yu Guo, Jianfei Huang, Yaqiong Xie, Shuanglei Yue, Minghui Chen, Hao Jiang, Mengjie Li
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. We explored the role of miR-200c in modulating the sensitivity of gefitinib-resistant NSCLC cells and examined the underlying mechanism. The gefitinib-resistant cell line PC-9-ZD and its parental PC-9 cells were used. Growth inhibition was detected by MTT assay. The cell apoptosis was detected by Annexin V/PI assay. Cell migration was assessed by wound-healing assay...
December 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27930702/a-survival-scoring-system-for-non-small-cell-lung-cancer-patients-with-de-novo-bone-metastases
#4
Yu-Mu Chen, Ying-Tang Fang, Chien-Hao Lai, Kun-Ming Rau, Cheng-Hua Huang, Huang-Chih Chang, Tung-Ying Chao, Chia-Cheng Tseng, Wen-Feng Fang, Chin-Chou Wang, Yung-Che Chen, Yu-Hsiu Chung, Yi-Hsi Wang, Mao-Chang Su, Shih-Feng Liu, Kuo-Tung Huang, Hung-Chen Chen, Ya-Chun Chang, Yu-Ping Chang, Meng-Chih Lin
In the pre-tyrosine kinase inhibitors (TKIs) era, non-small cell lung cancer (NSCLC) patients with de novo bone metastases had a worse prognosis than those without. However, whether epidermal growth factor receptor (EGFR)-TKIs affect the outcomes of EGFR mutant NSCLC patients with de novo bone metastases has not been well studied thus far. We retrospectively studied the effect of EGFR mutation status and first-line EGFR-TKIs on patient outcomes and created a survival scoring system for NSCLC patients with de novo bone metastases...
2016: PloS One
https://www.readbyqxmd.com/read/27928026/azd3759-a-bbb-penetrating-egfr-inhibitor-for-the-treatment-of-egfr-mutant-nsclc-with-cns-metastases
#5
Zhenfan Yang, Qiuli Guo, Yingchun Wang, Kan Chen, Lin Zhang, Ziqiang Cheng, Yanping Xu, Xiaolu Yin, Yu Bai, Sarit Rabbie, Dong-Wan Kim, Myung-Ju Ahn, James Chih-Hsin Yang, Xiaolin Zhang
Non-small-cell lung cancer patients with activating mutations in epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitor (TKI) treatment. Nevertheless, patients often develop central nervous system (CNS) metastases during treatment, even when their extracranial tumors are still under control. In the absence of effective options, much higher doses of EGFR TKIs have been attempted clinically, with the goal of achieving high enough drug concentrations within the CNS. Although limited tumor responses have been observed with this approach, the toxicities outside the CNS have been too high to tolerate...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27927060/new-data-on-clinical-decisions-in-nsclc-patients-with-uncommon-egfr-mutations
#6
Ting-Hui Wu, Emily Han-Chung Hsiue, Jih-Hsiang Lee, Chia-Chi Lin, James Chih-Hsin Yang
Non-small cell lung cancer patients harboring uncommon epidermal growth factor receptor (EGFR) mutations together account for approximately 10% of all EGFR mutations. The most common of which being G719X, S768I, L861Q, and exon 20 insertions. The clinical significance, particularly their response to EGFR tyrosine kinase inhibitors (TKIs) is largely unclear. Previous data is limited to a small fraction of patients in prospective studies and retrospective series. Recently, a combined analysis of patients with uncommon EGFR mutations in the Lux-Lung 2, Lux-Lung 3, Lux-Lung 6 trials provide new perspectives of uncommon EGFR mutations...
December 7, 2016: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/27926500/the-association-between-clinical-prognostic-factors-and-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-egfr-tki-efficacy-in-advanced-non-small-cell-lung-cancer-patients-a-retrospective-assessment-of-94-cases-with-egfr-mutations
#7
Jing-Hui Lin, Dong Lin, Ling Xu, Qiang Wang, Hui-Hua Hu, Hai-Peng Xu, Zhi-Yong He
OBJECTIVE: This study aimed to examine the association of clinical prognostic factors with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacy in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The demographic and clinical characteristics of 94 patients with stage IV NSCLC were retrospectively reviewed, and the association between clinical factors and EGFR-TKIs efficacy was evaluated. RESULTS: Of the 94 stage IV NSCLC patients enrolled in this study, a 74...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926485/axitinib-induces-senescence-associated-cell-death-and-necrosis-in-glioma-cell-lines-the-proteasome-inhibitor-bortezomib-potentiates-axitinib-induced-cytotoxicity-in-a-p21-waf-cip1-dependent-manner
#8
Maria Beatrice Morelli, Consuelo Amantini, Massimo Nabissi, Claudio Cardinali, Matteo Santoni, Giovanni Bernardini, Angela Santoni, Giorgio Santoni
Glioblastoma is associated with a poor overall survival despite new treatment advances. Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma.Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by γ-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines. Moreover, we found that p21(Waf1/Cip1) increased levels correlates with induction of ROS and senescence-associated cell death in U87 and T98 cell lines, which are reverted by N-acetyl cysteine pretreatment...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925256/pharmacokinetic-drug-drug-interactions-of-tyrosine-kinase-inhibitors-a-focus-on-cytochrome-p450-transporters-and-acid-suppression-therapy
#9
REVIEW
Caroline Gay, Delphine Toulet, Pascal Le Corre
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed...
December 7, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27924071/the-combination-therapy-of-imatinib-and-dasatinib-achieves-long-term-molecular-response-in-two-imatinib-resistant-and-dasatinibintolerant-patients-with-advanced-chronic-myeloid-leukemia
#10
Yu Zhu, Liangqin Pan, Ming Hong, Weixing Liu, Chun Qiao, Jianyong Li, Sixuan Qian
For patients with chronic myeloid leukemia (CML) failing imatinib therapy, second-generation tyrosine kinase inhibitors (TKIs) are recommended. Here, we describe two patients with advanced CML who failed imatinib therapy and did not tolerate the recommended dose of dasatinib, but then achieved a major molecular response with the combination of imatinib and dasatinib with no significant extramedullary toxicity. Our observations suggest that combination of TKIs may provide an additive/synergistic antileukemic effect...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27924059/an-open-label-phase-ii-study-evaluating-first-line-egfr-tyrosine-kinase-inhibitor-erlotinib-in-non-small-cell-lung-cancer-patients-with-tumors-showing-high-egfr-gene-copy-number
#11
Ewa Szutowicz-Zielińska, Krzysztof Konopa, Anna Kowalczyk, Małgorzata Suszko-Każarnowicz, Renata Duchnowska, Aleksandra Szczęsna, Magdalena Ratajska, Aleksander Sowa, Janusz Limon, Wojciech Biernat, Tomasz Burzykowski, Jacek Jassem, Rafał Dziadziuszko
BACKGROUND: First-line treatment with epidermal growth factor receptor (EGFR) inhibitors in NSCLC is effective in patients with activating EGFR mutations. The activity of erlotinib in patients harboring high EGFR gene copy number has been considered debatable. PATIENTS AND METHODS: A multicenter, open-label, single-arm phase II clinical trial was performed to test the efficacy of erlotinib in the first-line treatment of NSCLC patients harboring high EGFR gene copy number defined as ≥4 copies in ≥40% of cells...
December 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923714/brief-report-acquired-braf-v600e-mutation-as-resistant-mechanism-after-treatment-with-osimertinib
#12
Chao-Chi Ho, Wei-Yu Liao, Chih-An Lin, Jin-Yuan Shih, Chong-Jen Yu, James Chih-Hsin Yang
INTRODUCTION: AZD9291 (osimertinib) is designed for acquired T790M mutation after first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been used. Some of the resistance mechanisms that present after osimertinib treatment, including a newly acquired EGFR C797S mutation, have been identified. It is unclear, however, whether the bypass pathway is also a resistant mechanism in patients after osimertinib treatment. METHODS: Cells from malignant pleural effusion were collected and cultured at the time of progression in a patient being treated with osimertinib...
December 3, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27923629/prognostic-value-of-rare-and-complex-mutations-in-egfr-and-serum-levels-of-soluble-egfr-and-its-ligands-in-iranian-non-small-cell-lung-carcinoma-patients
#13
Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah Toutkaboni, Sharareh Seifi, Siamak Sabour, Abdolamir Allameh
BACKGROUND: A number of complex and rare mutations in epidermal growth factor receptor (EGFR) gene have been identified and the clinical implication of serum EGFR ligands has also been reported. However, the prognostic significance of these mutations and also the serum EGFR and its ligands in Non-Small Cell Lung Carcinoma (NSCLC) has remained a challenging issue. This study is aimed at finding the prognostic importance of EGFR rare mutations and serum EGFR, amphiregulin (AR), and TGF-α (Transforming Growth Factor-alpha) in NSCLC...
December 3, 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27922678/a-novel-rapid-point-of-care-test-for-lung-cancer-patients-to-detect-epidermal-growth-factor-receptor-gene-mutations-by-using-real-time-droplet-pcr-and-fresh-liquid-cytology-specimens
#14
Shiho Asaka, Akihiko Yoshizawa, Kazuyuki Matsuda, Akemi Yamaguchi, Hiroshi Yamamoto, Takayuki Shiina, Rie Nakata, Kaoru Ogawa, Meng Zhang, Takayuki Honda
Epidermal growth factor receptor gene (EGFR) mutations are associated with response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). We developed a novel, rapid EGFR mutation assay using a real-time droplet-polymerase chain reaction machine (EGFR d-PCR assay). The purpose of this study was to validate the performance of the EGFR d-PCR assay using fresh liquid cytology specimens. We analyzed three major EGFR mutations (L858R in exon 21, E746_A750del in exon 19 and T790M in exon 20) in 80 fresh liquid cytology specimens of adenocarcinoma (ADC) or NSCLC-not otherwise specified (NOS) via the EGFR d-PCR assay and conventional real-time PCR assay using the therascreen® EGFR RGQ PCR kit (Therascreen assay)...
December 2, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27920501/three-generations-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-developed-to-revolutionize-the-therapy-of-lung-cancer
#15
REVIEW
Haijun Zhang
Lung cancer, ~80%-85% of which is non-small-cell lung cancer (NSCLC), is the leading cause of cancer-related mortality worldwide. Sensitizing mutations in epidermal growth factor receptor (EGFR) gene (EGFRm(+)), such as exon 19 deletions and exon 21 L858R point mutations, are the most important drivers in NSCLC patients. In this respect, small-molecule EGFR tyrosine kinase inhibitors (TKIs) have been designed and developed, which launched the era of targeted, personalized and precise medicine for lung cancer...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27919989/teratogenic-effect-of-radotinib-case-report
#16
Juyoung Cheon, Jung Whan Ahn, Kyung Min Park, Guisera Lee, Yun Sung Jo
BACKGROUND: Simultaneous presentation of pregnancy and chronic myeloid leukemia (CML) is rare. Tyrosine kinase inhibitors (TKIs) are rarely used in pregnancy. There is almost no information on the effect of recently developed TKIs on the fetus. CASE REPORT: A 22-year-old woman became pregnant while using radotinib, a novel TKI for CML. She was concerned about the possible teratogenic effect of radotinib; hence the first pregnancy was terminated. The patient underwent full-term delivery at the second pregnancy...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27913578/characterization-of-egfr-t790m-l792f-and-c797s-mutations-as-mechanisms-of-acquired-resistance-to-afatinib-in-lung-cancer
#17
Yoshihisa Kobayashi, Koichi Azuma, Hiroki Nagai, Young Hak Kim, Yosuke Togashi, Yuichi Sesumi, Masato Chiba, Masaki Shimoji, Katsuaki Sato, Kenji Tomizawa, Toshiki Takemoto, Kazuto Nishio, Tetsuya Mitsudomi
Lung cancers harboring common EGFR mutations respond to EGFR tyrosine kinase inhibitors (TKIs). We previously reported that tumors with exon 18 mutations are particularly sensitive to irreversible second-generation (2G) afatinib compared with 1G-TKIs. However, data on the mechanisms of acquired resistance to afatinib are limited. We established afatinib-resistant cells by transfecting Ba/F3 cells with common or exon 18 (G719A and Del18) mutations and subjecting them to chronic exposure to increasing concentrations of afatinib...
December 2, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27913477/the-value-of-quality-of-life-assessment-in-chronic-myeloid-leukemia-patients-receiving-tyrosine-kinase-inhibitors
#18
Fabio Efficace, Laura Cannella
The development of the oral tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML) is one of the great triumphs of cancer research. Although the efficacy of TKIs has dramatically improved the disease-specific overall survival rate, the prevalence of CML is increasing worldwide. Currently, CML patients receive prolonged (even lifelong) treatment, and over the last decade, clinical decision making has become challenging. Therefore, consideration of the effects of TKI therapies on patients' quality of life (QoL) and symptom burden (ie, patient-reported outcomes [PROs]) is now critical to more robustly inform patient care and improve health care quality...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913476/chronic-myeloid-leukemia-sequencing-of-tki-therapies
#19
Jorge Cortes, Hagop Kantarjian
Multiple tyrosine kinase inhibitors (TKIs) are available for managing patients with chronic myeloid leukemia. Although most patients have a favorable outcome with their initial therapy, whether imatinib or a second-generation TKI was used, some will require subsequent use of one or more different TKIs. Such sequencing might be indicated in a reactive way (ie, for patients who have experienced resistance or intolerance to their initial therapy) or in a proactive way (ie, for patients with a somewhat favorable outcome who have not reached an "optimal" outcome)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913475/molecular-monitoring-in-chronic-myeloid-leukemia-how-low-can-you-go
#20
Susan Branford
Molecular monitoring of BCR-ABL1 transcripts for patients with chronic myeloid leukemia (CML) is now used to assess response to tyrosine kinase inhibitors (TKIs), including treatment failure that mandates a change of therapy. Therefore, many centers have adopted the molecular technique for measuring BCR-ABL1 and rely on conversion of values to the international reporting scale for appropriate clinical interpretation. However, the technique has a degree of inherent variability despite standardized procedures, which means care should be taken by the clinician when assessing response based on BCR-ABL1 cutoff limits...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
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