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Lindsay P Osborn, Philip R Cohen
Epidermal growth factor receptor (EGFR) inhibitors are biological factors used in the treatment of non-small-cell lung cancers (NSCLC) that are positive for EGFR mutations. Afatinib is one such drug that has been approved for use in this capacity. Cutaneous toxicity is the second most commonly reported adverse event with the use of afatinib. A 39-year-old woman with inoperative right lung adenocarcinoma was initially treated with afatinib. She not only developed a severe papulopustular eruption but also had a dramatic reduction of her tumor...
September 1, 2016: Curēus
Dominik Schulz, Markus Wirth, Guido Piontek, Anna Maria Stefanie Buchberger, Jürgen Schlegel, Rudolf Reiter, Gabriele Multhoff, Anja Pickhard
Despite remarkable successes with targeted therapies in the treatment of cancer, resistance can occur which limits the clinical outcome. In this study, we generated and characterized resistant cell clones derived from two different head and neck squamous cell carcinoma (HNSCC) cell lines (Cal27, UD-SCC-5) by long-term exposure to five targeted- and chemotherapeutics (afatinib, MK2206, BEZ235, olaparib and cisplatin). The resistant tumor cell clones showed an increased ERK1/2 expression and an altered expression of the stem-cell markers CD44, ALDH1, Oct4, Sox2, Nanog and Bmi1...
2016: American Journal of Cancer Research
Masayoshi Miyawaki, Hiroyuki Yasuda, Tetsuo Tani, Junko Hamamoto, Daisuke Arai, Kota Ishioka, Keiko Ohgino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Yuichiro Hayashi, Tomoko Betsuyaku, Kenzo Soejima
: Activation of the epidermal growth factor receptor (EGFR) pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib. Ceritinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLCs) harboring the ALK gene rearrangement. However, the precise mechanism underlying acquired resistance to ceritinib is not well defined. This study set out to clarify the mechanism in ALK-translocated lung cancer and to find the preclinical rationale overcoming EGFR pathway-induced acquired resistance to ALK-TKIs...
October 5, 2016: Molecular Cancer Research: MCR
Tetsuo Tani, Katsuhiko Naoki, Takanori Asakura, Toshiyuki Hirano, Shoji Suzuki, Keita Masuzawa, Hanako Hasegawa, Aoi Kuroda, Hiroyuki Yasuda, Makoto Ishii, Kenzo Soejima, Tomoko Betsuyaku
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-induced interstitial lung disease (ILD) may be a life-threatening condition that may develop during treatment of lung cancer patients harboring EGFR mutations. We herein present the case of a 41-year-old female patient diagnosed with lung adenocarcinoma with an EGFR mutation (exon 19 deletion). The patient was treated with gefitinib followed by erlotinib and developed ILD induced by both EGFR-TKIs; furthermore, the patient acquired resistance to EGFR-TKI treatment...
October 2016: Molecular and Clinical Oncology
Carlos H Barrios, Yi-Long Wu, James Chih-Hsin Yang, Lecia V Sequist, Sarayut L Geater, Tony Mok, Cheng-Ping Hu, Nobuyuki Yamamoto, Kenneth O'Byrne, Shun Lu, Vera Hirsh, Martin Sebastian, Isamu Okamoto, Riyaz Shah, Angela Märten, Dan Massey, Sven Wind, Martin Schuler
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
Santiago Ponce Aix, Keunchil Park, Eng-Huat Tan, Kenneth O'Byrne, Li Zhang, Michael Boyer, Tony Mok, Vera Hirsh, James Chih-Hsin Yang, Angela Märten, Luis Paz-Ares
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
Luis Fein, Yi-Long Wu, Lecia V Sequist, Sarayut L Geater, Sergey Orlov, Ki Hyeong Lee, Chun-Ming Tsai, Terufumi Kato, Katsuyuki Kiura, Carlos H Barrios, Martin Schuler, Vera Hirsh, Nobuyuki Yamamoto, Kenneth O'Byrne, Tony Mok, Dan Massey, Angela Märten, James Chih-Hsin Yang
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
L Warren, J C Turcotte, E Wehrenberg-Klee, G Oxnard, R H Mak, H Willers, L V Sequist
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Xiaochun Wang, David Goldstein, Philip J Crowe, Jia-Lin Yang
Tyrosine kinase inhibitors (TKIs) against human epidermal growth factor receptor (EGFR/HER) family have been introduced into the clinic to treat cancers, particularly non-small-cell lung cancer (NSCLC). There have been three generations of the EGFR/HER-TKIs. First-generation EGFR/HER-TKIs, binding competitively and reversibly to the ATP-binding site of the EGFR TK domain, show a significant breakthrough treatment in selected NSCLC patients with activating EGFR mutations (actEGFRm) EGFR (L858R) and EGFR (Del19), in terms of safety, efficacy, and quality of life...
2016: OncoTargets and Therapy
Elana J Fertig, Hiroyuki Ozawa, Manjusha Thakar, Jason D Howard, Luciane T Kagohara, Gabriel Krigsfeld, Ruchira S Ranaweera, Robert M Hughes, Jimena Perez, Siân Jones, Alexander V Favorov, Jacob Carey, Genevieve Stein-O'Brien, Daria A Gaykalova, Michael F Ochs, Christine H Chung
Patients with oncogene driven tumors are treated with targeted therapeutics including EGFR inhibitors. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates molecular alterations to EGFR, MAPK, and PI3K pathways in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to delineate interactions resulting from EGFR inhibitor use in cancer cells with these genetic alterations. We modify the HaCaT keratinocyte cell line model to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background...
September 16, 2016: Oncotarget
Tetsuya Mitsudomi, Yoshihisa Kobayashi
No abstract text is available yet for this article.
August 2016: Translational Lung Cancer Research
Xianfang Liu, Zhenghua Lv, Jidong Zou, Xiuxiu Liu, Juke Ma, Jinhua Wang, Na Sa, Peihang Jing, Wei Xu
Afatinib is the second generation of irreversible inhibitor of EGFR, HER2 and HER4, which has shown encouraging phase II and III clinical outcomes in the treatment of head and neck squamous cell carcinoma (HNSCC). However, the molecular mechanism of afatinib-induced apoptosis in HNSCC is poorly understood. In the present investigation, we discovered that down-regulation of MCL-1, an anti-apoptotic member of BCL-2 family, was responsible for afatinib-triggered apoptosis. And the inactivation of AKT-mTOR signaling caused by afatinib lead to translational inhibition of MCL-1 expression...
2016: American Journal of Cancer Research
Rolf W Sparidans, Hilde Rosing, Johannes J M Rood, Jan H M Schellens, Jos H Beijnen
No abstract text is available yet for this article.
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Feliciano Barron, Martha de la Torre-Vallejo, Rosa Luz Luna-Palencia, Andres F Cardona, Oscar Arrieta
INTRODUCTION: Lung cancer tumors present EGFR mutations associated with an increased response rate to tyrosine kinase inhibitors (TKIs). Afatinib acts as an irreversible pan-ErbB-TKI. AREAS COVERED: This review summarizes the results of clinical trials in NSCLC regarding its safety and efficacy. EXPERT OPINION: Afatinib in 40mg doses is highly effective in patients with NSCLC and EGFR mutations, improving progression-free survival and disease-related symptoms compared to chemotherapy...
September 16, 2016: Expert Opinion on Drug Safety
Antonio Passaro, Alessia Pochesci, Spitaleri Gianluca, Chiara Catania, Cristina Noberasco, Ester Del Signore, Filippo de Marinis
INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations are detected in about 10-15% of Caucasian and 30-40% of Asian patients with advanced or metastatic non-small-cell lung cancer (NSCLC). In patients harbouring EGFR mutations, the treatment with different available EGFR tyrosine kinase inhibitors (TKIs) showed to be more effective and safe than platinum-based chemotherapy regimens. AREAS COVERED: The current evidences about the role of afatinib for patients with EGFR-positive NSCLC are reviewed and discussed...
September 14, 2016: Expert Review of Clinical Pharmacology
J C-H Yang, L V Sequist, C Zhou, M Schuler, S L Geater, T Mok, C-P Hu, N Yamamoto, J Feng, K O'Byrne, S Lu, V Hirsh, Y Huang, M Sebastian, I Okamoto, N Dickgreber, R Shah, A Märten, D Massey, S Wind, Y-L Wu
BACKGROUND: Afatinib 40 mg/day is approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). In the case of drug-related grade ≥3 or selected prolonged grade 2 adverse events (AEs), the dose can be reduced by 10 mg decrements to a minimum of 20 mg. Here, we evaluate the influence of afatinib dose reduction on AEs, pharmacokinetics and progression-free survival (PFS) in the phase III LUX-Lung 3 and 6 (LL3/6) trials. PATIENTS AND METHODS: Treatment-naïve patients with advanced EGFR mutation-positive NSCLC in LL3 (global) and LL6 (China, Thailand, South Korea) were randomized to afatinib or chemotherapy...
September 6, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Soozana Puvanenthiran, Sharadah Essapen, Alan M Seddon, Helmout Modjtahedi
Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer stem cell (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), and HER family members and response to treatment with these agents...
September 5, 2016: International Journal of Oncology
(no author information available yet)
No abstract text is available yet for this article.
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Akimasa Sekine, Terufumi Kato, Tae Iwasawa, Tomohisa Baba, Akihiro Suido, Haruyasu Sakuranaka, Masaaki Futaki, Takashi Ogura
We herein report a case of a 67-year-old woman previously treated with erlotinib for adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation in exon 19, which rapidly developed to progressive symptomatic leptomeningeal carcinomatosis. The primary tumor and lung metastases also worsened and the performance status (PS) score declined to 3. With a re-biopsy from the pulmonary metastases, the T790M mutation was detected by the cobas EGFR mutation test, but not the cycleave test, although an exon 19 deletion was detected by both of the tests...
2016: Internal Medicine
Ana B Flórez, Marta Sierra, Patricia Ruas-Madiedo, Baltasar Mayo
Chemotherapy is a cornerstone of cancer treatment but it can have serious side effects, such as intestinal mucositis. This work reports the susceptibility/resistance profiles of 34 species of lactic acid bacteria (LAB), bifidobacteria and other intestinal bacteria from different collections to various chemotherapeutic agents (CAs) currently used in cancer treatments in an attempt to identify microorganisms that could prevent or treat mucositis symptoms. The highest concentrations of the CAs tested were equal to or higher than those reached in plasma during anticancer treatments...
August 18, 2016: International Journal of Antimicrobial Agents
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