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https://www.readbyqxmd.com/read/27913999/the-role-of-her2-egfr-and-other-receptor-tyrosine-kinases-in-breast-cancer
#1
Jennifer L Hsu, Mien-Chie Hung
Breast cancer affects approximately 1 in 8 women, and it is estimated that over 246,660 women in the USA will be diagnosed with breast cancer in 2016. Breast cancer mortality has decline over the last two decades due to early detection and improved treatment. Over the last few years, there is mounting evidence to demonstrate the prominent role of receptor tyrosine kinases (RTKs) in tumor initiation and progression, and targeted therapies against the RTKs have been developed, evaluated in clinical trials, and approved for many cancer types, including breast cancer...
December 2, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27913578/characterization-of-egfr-t790m-l792f-and-c797s-mutations-as-mechanisms-of-acquired-resistance-to-afatinib-in-lung-cancer
#2
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/27912836/epidermal-growth-factor-receptor-mutated-advanced-non-small-cell-lung-cancer-a-changing-treatment-paradigm
#3
REVIEW
Suchita Pakkala, Suresh S Ramalingam
Activating mutations in the epidermal growth factor receptor (EGFR) are present in approximately 15% of US patients with lung adenocarcinoma. EGFR tyrosine kinase inhibitors are associated with high response rate and progression-free survival for patients with non-small cell lung cancer with this genotype. Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912831/systemic-treatment-of-brain-metastases
#4
REVIEW
Saiama N Waqar, Daniel Morgensztern, Ramaswamy Govindan
Lung cancer continues to be the leading cause of cancer-related mortality in the United States. Brain metastases are a significant problem in patients with lung cancer and have conventionally been treated with whole-brain radiation. This article reviews the data for systemic chemotherapy to treat brain metastasis from lung cancer and examines the activity of small molecule tyrosine kinase inhibitors for the targeted therapy for brain metastases from EGFR-mutant and ALK-rearranged non-small cell lung cancer...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27912760/update-on-recent-preclinical-and-clinical-studies-of-t790m-mutant-specific-irreversible-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#5
REVIEW
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang
The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (1/2G EGFR-TKIs) gefitinib, erlotinib, and afatinib have all been approved as standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer. The third-generation (3G) EGFR-TKIs have been developed to overcome the EGFR T790M mutation, which is the most common mechanism of acquired resistance to 1/2G EGFR-TKI treatment. This resistance mutation develops in half of the patients who respond to 1/2G EGFR-TKI therapy...
December 3, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27910964/osimertinib-a-third-generation-tyrosine-kinase-inhibitor-targeting-non-small-cell-lung-cancer-with-egfr-t790m-mutations
#6
C E McCoach, A Jimeno
Oncogenic driver mutations in the epidermal growth factor receptor (EGFR) gene have provided a focus for effective targeted therapy. Unfortunately, all patients eventually develop resistance to frontline therapy with EGFR tyrosine kinase inhibitors (TKIs). The majority of patients develop a large subclonal population of tumor cells with a T790M mutation that renders these cells resistant to first-generation TKIs. Osimertinib is a third-generation EGFR TKI that was designed to overcome resistance from T790M mutations...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910913/loss-of-egfr-asap1-signaling-in-metastatic-and-unresectable-hepatoblastoma
#7
Sarangarajan Ranganathan, Mylarappa Ningappa, Chethan Ashokkumar, Brandon W Higgs, Jun Min, Qing Sun, Lori Schmitt, Shankar Subramaniam, Hakon Hakonarson, Rakesh Sindhi
Hepatoblastoma (HBL), the most common childhood liver cancer is cured with surgical resection after chemotherapy or with liver transplantation if local invasion and multifocality preclude resection. However, variable survival rates of 60-80% and debilitating chemotherapy sequelae argue for more informed treatment selection, which is not possible by grading the Wnt-β-catenin over activity present in most HBL tumors. A hypothesis-generating whole transcriptome analysis shows that HBL tumors removed at transplantation are enriched most for cancer signaling pathways which depend predominantly on epidermal growth factor (EGF) signaling, and to a lesser extent, on aberrant Wnt-β-catenin signaling...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910740/oral-squamous-cell-carcinoma-current-treatment-strategies-and-nanotechnology-based-approaches-for-prevention-and-therapy
#8
Sankalp A Gharat, Munira Momin, Chintan Bhavsar
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer; it involves damage to oral epithelial cells due to accumulation of multiple genetic mutations in the cells. OSCC remains major cause of morbidity and mortality in patients with head and neck cancers. Tobacco, smoking, alcohol consumption alone or with chewing tobacco, and betel quid are potential carcinogens contributing to the high occurrence of OSCC. Current treatment modalities for OSCC like chemoradiotherapy, surgery, EGFR inhibitors and COX-2 inhibitors, and photodynamic therapy have led to the major problems related to non-specific cell death...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27908760/affibody-displaying-bio-nanocapsules-effective-in-egfr-typical-biomarker-expressed-in-various-cancer-cells
#9
Yuya Nishimura, Ryosuke Ezawa, Jun Ishii, Chiaki Ogino, Akihiko Kondo
The expression of epidermal growth factor receptor (EGFR) across a wide range of tumor cells has attracted attention for use as a tumor marker in drug delivery systems. Therefore, binding molecules with the ability to target EGFR have been developed. Among them, we focused on affibodies that are binding proteins derived from staphylococcal protein A. By displaying affibody (ZEGFR) binding to EGFR on the surface of a bio-nanocapsule (BNC) derived from a hepatitis B virus (HBV), we developed an altered BNC (ZEGFR-BNC) with a high specificity to EGFR-expressing cells...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27908290/bile-acid-a-potential-inducer-of-colon-cancer-stem-cells
#10
Lulu Farhana, Pratima Nangia-Makker, Evan Arbit, Kathren Shango, Sarah Sarkar, Hamidah Mahmud, Timothy Hadden, Yingjie Yu, Adhip P N Majumdar
BACKGROUND: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. METHODS: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27907909/egfr-kinase-inhibitors-and-gastric-acid-suppressants-in-egfr-mutant-nsclc-a-retrospective-database-analysis-of-potential-drug-interaction
#11
Nesaretnam Barr Kumarakulasinghe, Nicholas Syn, Yu Yang Soon, Atasha Asmat, Huili Zheng, En Yun Loy, Brendan Pang, Ross Andrew Soo
BACKGROUND: Erlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907852/the-relevance-of-primary-tumour-location-in-patients-with-metastatic-colorectal-cancer-a-meta-analysis-of-first-line-clinical-trials
#12
Julian Walter Holch, Ingrid Ricard, Sebastian Stintzing, Dominik Paul Modest, Volker Heinemann
BACKGROUND: Retrospective subgroup analyses suggest that primary tumour location (PTL) has a prognostic importance and relates to response to targeted therapy. METHODS: We conducted a meta-analysis of first-line clinical trials available up to October 2016, which assessed the relevance of PTL in patients with metastatic colorectal cancer (mCRC). Right- and left-sided colorectal cancers were differentiated (RC and LC). RESULTS: In 13 first-line randomised controlled trials and one prospective pharmacogenetic study, RC was associated with a significantly worse prognosis compared with LC (hazard ratio [HR] for overall survival: 1...
November 28, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27906420/the-effect-of-low-dosage-of-procaine-on-lung-cancer-cell-proliferation
#13
X-W Ma, Y Li, X-C Han, Q-Z Xin
OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common type of human lung cancer leading cause of cancer death worldwide. However, first-line drugs such as gefitinib and erlotinib showed great drug resistance in the clinical. MATERIALS AND METHODS: The cell proliferation was evaluated by MTT assay; gene expression was detected by qPCR assay. The protein expression was analyzed by Western blotting. RESULTS: Our results showed that in mouse models of lung cancer by A549 or NCI-H1975 xenograft, the local anesthetic drug Procaine (PCA) with 50 mg/kg specifically attenuated tumors compared with the vehicle-treated group...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27905549/corrigendum-egfr-tyrosine-kinase-inhibitors-versus-chemotherapy-as-first-line-therapy-for-non-small-cell-lung-cancer-patients-with-the-l858r-point-mutation
#14
Jianlin Xu, Haitang Yang, Bo Jin, Yuqing Lou, Yanwei Zhang, Xueyan Zhang, Hua Zhong, Huiming Wang, Dan Wu, Baohui Han
No abstract text is available yet for this article.
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905110/distinct-molecular-landscapes-between-endometrioid-and-non-endometrioid-uterine-carcinomas
#15
Nathaniel L Jones, Joanne Xiu, Sudeshna Chatterjee-Paer, Alexandre Buckley de Meritens, William M Burke, Ana I Tergas, Jason D Wright, June Y Hou
Endometrial carcinoma (EC) is traditionally characterized as endometrioid and non-endometrioid based on histo-pathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27903975/cortactin-promotes-colorectal-cancer-cell-proliferation-by-activating-the-egfr-mapk-pathway
#16
Xiaojian Zhang, Kun Liu, Tao Zhang, Zhenlei Wang, Xuan Qin, Xiaoqian Jing, Haoxuan Wu, Xiaopin Ji, Yonggang He, Ren Zhao
Cortactin (CTTN) is overexpressed in various tumors, including head and neck squamous cell carcinoma and colorectal cancer (CRC), and can serve as a biomarker of cancer metastasis. We observed that CTTN promotes cancer cell proliferation in vitro and increases CRC tumor xenograft growth in vivo. CTTN expression increases EGFR protein levels and enhances the activation of the MAPK signaling pathway. CTTN expression also inhibits the ubiquitin-mediated degradation of EGFR by suppressing the coupling of c-Cbl with EGFR...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902470/phase-i-study-of-qlnc120-a-novel-egfr-and-her2-kinase-inhibitor-in-pre-treated-patients-with-her2-overexpressing-advanced-breast-cancer
#17
Tongtong Zhang, Qing Li, Shanshan Chen, Yang Luo, Ying Fan, Binghe Xu
This study evaluated the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic profile, and preliminary antitumor activity of QLNC120, an inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), in HER2 overexpressing advanced breast cancer patients. In addition, the prognostic biomarkers of QLNC120 were investigated. QLNC120 was administered as a single dose, followed by 7 days observation, and then once daily consecutively. Scheduled dose escalation was 450mg, 750mg, 1000mg and 1250mg...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902463/novel-multi-targeted-erbb-family-inhibitor-afatinib-blocks-egf-induced-signaling-and-induces-apoptosis-in-neuroblastoma
#18
Xinfang Mao, Zhenghu Chen, Yanling Zhao, Yang Yu, Shan Guan, Sarah E Woodfield, Sanjeev A Vasudevan, Ling Tao, Jonathan C Pang, Jiaxiong Lu, Huiyuan Zhang, Fuchun Zhang, Jianhua Yang
Neuroblastoma is the most common extracranial solid tumor in children. The ErbB family of proteins is a group of receptor tyrosine kinases that promote the progression of various malignant cancers including neuroblastoma. Thus, targeting them with small molecule inhibitors is a promising strategy for neuroblastoma therapy. In this study, we investigated the anti-tumor effect of afatinib, an irreversible inhibitor of members of the ErbB family, on neuroblastoma. We found that afatinib suppressed the proliferation and colony formation ability of neuroblastoma cell lines in a dose-dependent manner...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900942/association-between-chronic-kidney-disease-and-cancer-mortality-a-report-from-the-allhat
#19
Dhruti P Chen, Barry R Davis, Lara M Simpson, William C Cushman, Jeffrey A Cutler, Mirela Dobre, Charles E Ford, Gail T Louis, Paul Muntner, Suzanne Oparil, Linda B Piller, Sara L Pressel, Mark J Sarnak, Paul K Whelton, Jackson T Wright, Mahboob Rahman
BACKGROUND/OBJECTIVES: Chronic kidney disease (CKD) and cancer are both common in older patients; whether CKD increases risk for cancer is unclear. This study evaluated CKD as a risk factor for cancer mortality in a large cohort of hypertensive patients. STUDY DESIGN: We did post-hoc analyses of in-trial and post-trial data from participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). SETTING AND PARTICIPANTS: Participants were ≥ 55 years old with hypertension and one other additional risk factor for coronary heart disease...
November 30, 2016: Clinical Nephrology
https://www.readbyqxmd.com/read/27900441/successful-afatinib-treatment-of-advanced-non-small-cell-lung-cancer-patients-undergoing-hemodialysis
#20
Hisao Imai, Kyoichi Kaira, Ichiro Naruse, Hideki Hayashi, Hirotoshi Iihara, Yutaro Kita, Naoki Mizusaki, Takayuki Asao, Yoshinori Itoh, Tadashi Sugiyama, Koichi Minato, Masanobu Yamada
The treatment for patients with lung cancer undergoing hemodialysis, who are frequently elderly and have poor performance status, becomes a more important subject. However, the feasibility of afatinib in patients with chronic renal failure undergoing hemodialysis has not, so far, been reported. Here, afatinib was administered to three patients with NSCLC harboring EGFR mutation and chronic renal failure undergoing hemodialysis. Pharmacokinetic (PK) data of afatinib supported the safety of afatinib treatment...
November 29, 2016: Cancer Chemotherapy and Pharmacology
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