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https://www.readbyqxmd.com/read/30321910/epidermal-growth-factor-receptor-blockers-for-the-treatment-of-ovarian-cancer
#1
REVIEW
Jo Morrison, Clemens Thoma, Richard J Goodall, Thomas J Lyons, Kezia Gaitskell, Alison J Wiggans, Andrew Bryant
BACKGROUND: This is an update of a previously published version of the review (Issue 10, 2011).Epithelial ovarian cancer (EOC) is the seventh most common cause of cancer death among women worldwide. Treatment consists of a combination of surgical debulking and platinum-based chemotherapy. Between 55% and 75% of women who respond to first-line therapy experience relapse within two years. Second-line chemotherapy is palliative and aims to reduce symptoms and prolong survival. Improved understanding about the molecular basis of EOC has led to the development of novel agents, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and anti-EGFR antibodies...
October 16, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/30317423/mucin-2-muc2-modulates-the-aggressiveness-of-breast-cancer
#2
Anna Astashchanka, Thomas M Shroka, Britta M Jacobsen
PURPOSE: Tumors that secrete large volumes of mucus are chemotherapy resistant, however, mechanisms underlying this resistance are unknown. One protein highly expressed in mucin secreting breast cancers is the secreted mucin, Mucin 2 (MUC2). While MUC2 is expressed in some breast cancers it is absent in normal breast tissue, implicating it in breast cancer. However, the effects of MUC2 on breast cancer are largely unknown. This study examined the role of MUC2 in modulating breast cancer proliferation, response to chemotherapy and metastasis...
October 13, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/30315932/ym155-sensitizes-non-small-cell-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitors-through-the-mechanism-of-autophagy-induction
#3
Chun-Hua Dai, Yang Shu, Ping Chen, Jian-Nong Wu, Li-Haun Zhu, Rong-Xia Yuan, Wei-Guo Long, Yu-Min Zhu, Jian Li
Resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib and gefitinib, is a major clinical problem in the treatment of patients with non-small cell lung cancer (NSCLC). YM155 is a survivin small molecule inhibitor and has been demonstrated to induce cancer cell apoptosis and autophagy. EGFR-TKIs have been known to induce cancer cell autophagy. In this study, we showed that YM155 markedly enhanced the sensitivity of erlotinib to EGFR-TKI resistant NSCLC cell lines H1650 (EGFR exon 19 deletion and PTEN loss) and A549 (EGFR wild type and KRAS mutation) through inducing autophagy-dependent apoptosis and autophagic cell death...
October 10, 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30305724/quantitative-proteomics-analysis-identifies-muc1-as-an-effect-sensor-of-egfr-inhibition
#4
H Rudolf de Boer, Martin Pool, Esméé Joosten, Marieke Everts, Douwe F Samplonius, Wijnand Helfrich, Harry J M Groen, Suzanne van Cooten, Fabrizia Fusetti, Rudolf S N Fehrmann, Elisabeth G E de Vries, Marcel A T M van Vugt
Tumor responses to cancer therapeutics are generally monitored every 2-3 months based on changes in tumor size. Dynamic biomarkers that reflect effective engagement of targeted therapeutics to the targeted pathway, so-called "effect sensors", would fulfill a need for non-invasive, drug-specific indicators of early treatment effect. Using a proteomics approach to identify effect sensors, we demonstrated MUC1 upregulation in response to epidermal growth factor receptor (EGFR)-targeting treatments in breast and lung cancer models...
October 10, 2018: Oncogene
https://www.readbyqxmd.com/read/30302022/an-her3-targeting-antibody-drug-conjugate-incorporating-a-dna-topoisomerase-i-inhibitor-u3-1402-conquers-egfr-tyrosine-kinase-inhibitor-resistant-nsclc
#5
Kimio Yonesaka, Naoki Takegawa, Satomi Watanabe, Koji Haratani, Hisato Kawakami, Kazuko Sakai, Yasutaka Chiba, Naoyuki Maeda, Takashi Kagari, Kenji Hirotani, Kazuto Nishio, Kazuhiko Nakagawa
EGFR tyrosine kinase inhibitors (TKIs) are standard therapy for EGFR-mutant non-small cell lung cancer (NSCLC); however, these tumours eventually acquire chemoresistance. U3-1402 is an anti-HER3 antibody-drug conjugate with a novel topoisomerase I inhibitor, DXd. In the current study, we evaluated the anticancer efficacy of U3-1402 in EGFR-mutant NSCLC cells with acquired resistance to EGFR-TKIs. HCC827GR5 and PC9AZDR7 are EGFR-TKI-resistant clones for gefitinib and osimertinib, respectively. U3-1402 alone or in combination with the EGFR-TKI erlotinib demonstrated potent anticancer efficacy in HCC827GR5 cells using an in vitro growth inhibition assay and in vivo xenograft mouse model...
October 9, 2018: Oncogene
https://www.readbyqxmd.com/read/30296375/erlotinib-guided-self-assembled-trifunctional-click-nanotheranostics-for-distinguishing-druggable-mutations-and-synergistic-therapy-of-nsclc
#6
Yu Gao, Huijuan Zhang, Yingying Zhang, Tingting Lv, Lu Zhang, Ziying Li, Xiaodong Xie, Fengqiao Li, Haijun Chen, Lee Jia
The outcome of molecular targeted therapies is restricted by the ambiguous molecular subtypes of non-small cell lung cancer (NSCLC) which are difficult to be defined with druggable mutations, and the inevitable emergence of drug-resistance. Here we used the Cu-catalyzed click chemistry to synthesize a chitosan-based self-assembled nanotheranostics (CE7Ns) composing of a near-infrared (NIR) fluorescent photosensitizer Cy7 and molecular targeted drug erlotinib. The well-characterized CE7Ns can release erlotinib and Cy7 fast under acidic condition in the presence of lysozyme, distinguish three molecular subtypes of NSCLC and specifically bind to the erlotinib-sensitive EGFR-mutated PC-9 cells...
October 8, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/30288054/immunotherapy-combined-with-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-treatment
#7
REVIEW
Hongge Liang, Xiaoyan Liu, Mengzhao Wang
In recent years, targeted therapy and immunotherapy have played important roles in the treatment of patients with non-small-cell lung cancer (NSCLC). Drugs that target epidermal growth factor receptor (EGFR) mutations (eg, gefitinib, erlotinib, icotinib, and osimertinib) are among the most commonly used targeted therapies. Afatinib is an irreversible second-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI), and the LUX-Lung 3 trial demonstrated the superiority of afatinib to cisplatin and pemetrexed in the frontline treatment of treatment-naïve patients with advanced EGFR mutation adenocarcinoma of the lung...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/30284706/egfr-amplification-and-sensitizing-mutations-correlate-with-survival-in-lung-adenocarcinoma-patients-treated-with-erlotinib-mutp-clicap
#8
Alejandro Ruiz-Patiño, Christian David Castro, Luisa María Ricaurte, Andrés F Cardona, Leonardo Rojas, Zyanya Lucia Zatarain-Barrón, Beatriz Wills, Noemí Reguart, Hernán Carranza, Carlos Vargas, Jorge Otero, Luis Corrales, Claudio Martín, Pilar Archila, July Rodriguez, Jenny Avila, Melissa Bravo, Luis Eduardo Pino, Rafael Rosell, Oscar Arrieta
BACKGROUND: Non-small cell lung cancer (NSCLC) has a 5-year survival of 5-16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role. OBJECTIVE: Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp...
October 2018: Targeted Oncology
https://www.readbyqxmd.com/read/30275271/retraction-apoptosis-inducing-effect-of-erlotinib-is-potentiated-by-3-3-diindolylmethane-in-vitro-and-in-vivo-using-an-orthotopic-model-of-pancreatic-cancer
#9
(no author information available yet)
No abstract text is available yet for this article.
October 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/30271827/team-management-of-skin-rash-associated-with-use-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#10
Katsuhiro Masago, Fumiko Imamichi, Yoshio Masuda, Noriko Ariga, Kiyomi Fujitomi, Yoko Fukumine, Kana Hatakenaka, Shiro Fujita, Nobuyuki Katakami
Objective: The aim of this study was to evaluate the effectiveness of a rash team management intervention designed by certified nurses, medical physicians, and certified pharmacists. The quality of life (QOL) of patients administered epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) was assessed using the dermatology life quality index (DLQI) and Skindex-29 QOL questionnaires. Methods: A total of 51 patients with nonsmall cell lung cancer who were treated using EGFR-TKIs were examined between November 1, 2014, and October 31, 2015, at the Institute of Biomedical Research and Innovation in Kobe city, Japan...
October 2018: Asia-Pacific Journal of Oncology Nursing
https://www.readbyqxmd.com/read/30268462/high-throughput-sequencing-reveals-distinct-genetic-features-and-clinical-implications-of-nsclc-with-de-novo-and-acquired-egfr-t790m-mutation
#11
Panwen Tian, Ye Wang, Weiya Wang, Yalun Li, Ke Wang, Xiaowei Cheng, Yuan Tang, Han Han-Zhang, Junyi Ye, Shannon Chuai, Weimin Li
INTRODUCTION: De novo T790 M mutation in EGFR has been reported in various studies. However, its genetic characteristics and association with EGFR tyrosine kinase inhibitors (TKIs) treatment response remain poorly studied. METHODS: We retrospectively screened 1228 consecutive non-small cell lung cancer (NSCLC) patients and identified 29 de novo T790 M carriers. Capture-based targeted deep sequencing was conducted on 21 eligible samples as well as a 20-sample cohort with acquired T790 M mutation after EGFR-TKIs treatment...
October 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/30263066/preventing-and-treating-brain-metastases-with-three-first-line-egfr-tyrosine-kinase-inhibitors-in-patients-with-egfr-mutation-positive-advanced-non-small-cell-lung-cancer
#12
Po-Lan Su, Yi-Lin Wu, Wei-Yuan Chang, Chung-Liang Ho, Yau-Lin Tseng, Wu-Wei Lai, Wu-Chou Su, Chien-Chung Lin, Szu-Chun Yang
Introduction: Brain metastases (BM) are common in advanced non-small cell lung cancer (NSCLC), and the prognosis is poor with few therapeutic options. This study evaluated the efficacy of three epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in preventing and treating BM in patients with EGFR mutation-positive advanced NSCLC. Methods: Patients with EGFR mutation-positive advanced NSCLC who visited a tertiary referral center from 1 December 2013 to 30 November 2017 were analyzed retrospectively...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/30255614/sensitivity-of-epidermal-growth-factor-receptor-with-single-or-double-uncommon-mutations-to-afatinib-confirmed-by-a-visual-assay
#13
Shinichi Kimura, Kentaro Tanaka, Taishi Harada, Renpeng Liu, Daisuke Shibahara, Yuko Kawano, Yoichi Nakanishi, Isamu Okamoto
Patients with non-small cell lung cancer (NSCLC) harboring common mutations of the epidermal growth factor receptor (EGFR) are sensitive to EGFR-tyrosine kinase inhibitors (TKI). Although forms of EGFR harboring single uncommon mutations such as G719X or L861Q are thought to be less sensitive to EGFR-TKI, the efficacy of these drugs in patients with double uncommon mutations has remained unclear. We here present an NSCLC patient found to be positive for double uncommon EGFR mutations (G719X and L861Q) by clinical genomic sequencing analysis of a pleural effusion specimen who showed a durable response to the EGFR-TKI afatinib...
September 25, 2018: Cancer Science
https://www.readbyqxmd.com/read/30254074/structures-of-human-cytochrome-p450-1a1-with-bergamottin-and-erlotinib-reveal-active-site-modifications-for-binding-of-diverse-ligands
#14
Aaron G Bart, Emily E Scott
Human cytochrome P450 1A1 (CYP1A1) is an extrahepatic enzyme involved in the monooxygenation of structurally-diverse compounds ranging from natural products to drugs and protoxins.  Because CYP1A1 has a role in human carcinogenesis, inhibiting its activity may potentially aid in cancer chemoprevention, whereas utilizing CYP1A1's oxidative activity could help selectively activate anticancer prodrugs. Such potential therapeutic purposes require detailed knowledge of CYP1A1's interactions with potential ligands...
September 25, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30243717/induction-of-apoptosis-by-morusin-in-human-non-small-cell-lung-cancer-cells-by-suppression-of-egfr-stat3-activation
#15
Hyun-Ji Park, Tae-Rin Min, Gyoo-Yong Chi, Yung-Hyun Choi, Shin-Hyung Park
This study was designed to validate the anticancer effects of morusin in human non-small cell lung cancer (NSCLC) cells. Morusin suppressed the cell growth and colony formation in a concentration-dependent manner in H1299, H460 and H292 cells. These anticancer activities were related with apoptosis induction proved by the accumulation of chromatin condensation, PARP cleavage, increase of sub-G1 phage and annexin V-positive cell population. Interestingly, signal transducer and activator of transcription 3 (STAT3) was dephosphorylated by morusin...
September 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30242021/a-high-throughput-immune-oncology-screen-identifies-egfr-inhibitors-as-potent-enhancers-of-antigen-specific-cytotoxic-t-lymphocyte-tumor-cell-killing
#16
Patrick H Lizotte, Ruey-Long Hong, Troy A Luster, Megan E Cavanaugh, Luke J Taus, Stephen Wang, Abha Dhaneshwar, Naomi Mayman, Aaron Yang, Meghana Kulkarni, Lauren Badalucco, Erica Fitzpatrick, Hsiang-Fong Kao, Mari Kuraguchi, Mark Bittinger, Paul T Kirschmeier, Nathanael S Gray, David A Barbie, Pasi A Jänne
We developed a screening assay in which luciferized ID8 expressing OVA was cocultured with transgenic CD8+ T cells specifically recognizing the model antigen in an H-2b-restricted manner. The assay was screened with a small-molecule library to identify compounds that inhibit or enhance T cell-mediated killing of tumor cells. Erlotinib, an EGFR inhibitor, was the top compound that enhanced T-cell killing of tumor cells. Subsequent experiments with erlotinib and additional EGFR inhibitors validated the screen results...
September 21, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/30241558/effects-of-repurposed-drug-candidates-nitroxoline-and-nelfinavir-as-single-agents-or-in-combination-with-erlotinib-in-pancreatic-cancer-cells
#17
Serena Veschi, Laura De Lellis, Rosalba Florio, Paola Lanuti, Alberto Massucci, Nicola Tinari, Michele De Tursi, Pierluigi di Sebastiano, Marco Marchisio, Clara Natoli, Alessandro Cama
BACKGROUND: Pancreatic cancer (PC) is the fourth most common cause of cancer death. Combination therapies with classical chemotherapeutic agents improved treatment of advanced PC at the cost of a relevant toxicity, but the 5-year survival rate remains below 5%. Consequently, new therapeutic options for this disease are urgently needed. In this study, we explored the effect of two repurposed drug candidates nelfinavir and nitroxoline, approved for non-anticancer human use, in PC cell lines...
September 21, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/30240852/osimertinib-versus-standard-of-care-egfr-tki-as-first-line-treatment-in-patients-with-egfrm-advanced-nsclc-flaura-asian-subset
#18
Byoung Chul Cho, Busayamas Chewaskulyong, Ki Hyeong Lee, Arunee Dechaphunkul, Virote Sriuranpong, Fumio Imamura, Naoyuki Nogami, Takayasu Kurata, Isamu Okamoto, Caicun Zhou, Ying Cheng, Eun Kyung Cho, Pei Jye Voon, Jong-Seok Lee, Helen Mann, Matilde Saggese, Thanyanan Reungwetwattana, Suresh S Ramalingam, Yuichiro Ohe
INTRODUCTION: Here we report efficacy and safety data of an Asian subset of the Phase III FLAURA trial (NCT02296125), which compares osimertinib with standard-of-care (SoC) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with previously untreated advanced non-small cell lung cancer (NSCLC) with tumors harboring exon 19 deletion (Ex19del)/L858R EGFR-TKI sensitizing mutations (EGFRm). METHODS: Eligible Asian patients (enrolled at Asian sites) ≥18 years (≥20 years in Japan), with untreated EGFRm advanced NSCLC were randomized 1:1 to receive osimertinib (80 mg orally, once daily [qd]) or SoC EGFR-TKI (gefitinib [250 mg] or erlotinib [150 mg] orally, qd)...
September 18, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/30240496/design-of-a-multicompartment-hydrogel-that-facilitates-time-resolved-delivery-of-combination-therapy-and-synergized-killing-of-glioblastoma
#19
Poulami Majumder, Ulrich Baxa, Scott Tr Walsh, Joel P Schneider
There is significant current interest in identifying new combination therapies that synergize to treat disease, and it is becoming increasingly clear that the temporal resolution of their administration greatly impacts efficacy.To facilitate effective delivery, we developed a multicompartment hydrogel material composed of spherical vesicles interlaced within a self-assembled peptide-based network of physically crosslinked fibrils that allows time-resolved independent co-delivery of small molecules. Herein, we demonstrate that this material architecture effectively delivers the EGFR kinase inhibitor erlotinib (ERL) and doxorubicin (DOX, DNA intercalator) in an ERL_DOX sequential manner to synergistically kill glioblastoma, the most aggressive form of brain cancer...
September 21, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/30233210/suppression-of-c-met-overcomes-erlotinib-resistance-in-tongue-cancer-cells
#20
Keqiang Huang, Dongxu Liu
Background: Erlotinib is a commonly used molecular-targeted drug for the treatment of tongue cancer. However, the development of acquired resistance to erlotinib hampers its therapeutic use. Materials and methods: To analyze the erlotinib resistance, long-term and short term survival assay were used to compare the resistance between parental and resistant tongue cancer cells. Flow cytometry, Hochest staining and western blot were used to analyze the apoptosis among the cells...
2018: OncoTargets and Therapy
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