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https://www.readbyqxmd.com/read/28331003/phase-i-dose-escalation-study-of-taselisib-gdc-0032-an-oral-pi3k-inhibitor-in-patients-with-advanced-solid-tumors
#1
Dejan Juric, Ian Krop, Ramesh K Ramanathan, Timothy R Wilson, Joseph A Ware, Sandra Sanabria Bohorquez, Heidi Savage, Deepak Sampath, Laurent Salphati, Ray Lin, Huan Jin, Hema Parmar, Jerry Y Hsu, Daniel D Von Hoff, José Baselga
Taselisib is a potent and selective tumor growth inhibitor through PI3K pathway suppression. Thirty-four patients with locally advanced or metastatic solid tumors were treated (phase I study, modified 3+3 dose escalation; 5 cohorts; 3-16 mg taselisib once daily capsule). Taselisib pharmacokinetics were dose-proportional; mean half-life was 40 hours. Frequent dose-dependent, treatment-related adverse events included diarrhea, hyperglycemia, decreased appetite, nausea, rash, stomatitis, and vomiting. At 12 and 16 mg dose levels, dose limiting toxicities (DLT) were observed, with an accumulation of higher-grade adverse events after the cycle 1 DLT assessment window...
March 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28325292/sirna-encapsulated-hybrid-nanoparticles-target-mutant-k-ras-and-inhibit-metastatic-tumor-burden-in-a-mouse-model-of-lung-cancer
#2
Maryna Perepelyuk, Olubunmi Shoyele, Ruth Birbe, Chellappagounder Thangavel, Yi Liu, Robert B Den, Adam E Snook, Bo Lu, Sunday A Shoyele
There is an unmet need in the development of an effective therapy for mutant K-ras-expressing non-small-cell lung cancer (NSCLC). Although various small molecules have been evaluated, an effective therapy remains a dream. siRNAs have the potential to downregulate mutant K-ras both at the protein and mRNA levels. However, a safe and effective delivery of siRNAs to tumors remains a limitation to their translational application in the treatment of this highly debilitating disease. Here we developed a novel hybrid nanoparticle carrier for effective delivery of anti-mutant K-ras to NSCLC (AKSLHN)...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28323493/microparticles-containing-erlotinib-loaded-solid-lipid-nanoparticles-for-treatment-of-non-small-cell-lung-cancer
#3
Zahra Bakhtiary, Jaleh Barar, Ayuob Aghanejad, Amir Ata Saei, Elhameh Nemati, Jafar Ezzati Nazhad Dolatabadi, Yadollah Omidi
Non-small cell lung cancer (NSCLC) patients with sensitizing mutations in the exons 18-21 of the epithelial growth factor receptor (EGFR) geneshowincreased kinase activity of EGFR. Hence, tyrosine kinase inhibitors (TKIs) such as erlotinib (ETB) havecommonly been used as the second line therapeutic option in metastatic NSCLC. While the ETB is available as an oral dosage form, the local delivery of this TKI to the diseased cells of the lung may ameliorate its therapeutic impacts. In the current study, we report on the development of ETB-loaded solid lipid nanoparticle (SLN) based formulation of dry powder inhaler (ETB-SLN DPI)...
March 21, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28321814/immunotherapy-in-nsclc-a-promising-and-revolutionary-weapon
#4
Christian Rolfo, Christian Caglevic, Mariacarmela Santarpia, Antonio Araujo, Elisa Giovannetti, Carolina Diaz Gallardo, Patrick Pauwels, Mauricio Mahave
Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. Targeted therapies for EGFR and ALK mutant patients have showed better results when compared with chemotherapy, nevertheless most of patients will fail and need to be treated with chemotherapy if they still have a good performance status...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28293124/spotlight-on-necitumumab-in-the-treatment-of-non-small-cell-lung-carcinoma
#5
REVIEW
Manish K Thakur, Antoinette J Wozniak
The treatment options for metastatic non-small-cell lung cancer (NSCLC) have expanded dramatically in the last 10 years with the discovery of newer drugs and targeted therapy. Epidermal growth factor receptor (EGFR), when aberrantly activated, promotes cell growth and contributes in various ways to the malignant process. EGFR has become an important therapeutic target in a variety of malignancies. Small-molecule tyrosine kinase inhibitors (TKIs) of EGFR are being used to treat advanced NSCLC and are particularly effective in the presence of EGFR mutations...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28293123/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-patient-selection-and-perspectives
#6
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28289866/the-role-of-circulating-tumor-cells-in-evaluation-of-prognosis-and-treatment-response-in-advanced-non-small-cell-lung-cancer
#7
Jia Zhou, Fei Dong, Fang Cui, Rui Xu, Xiaokui Tang
PURPOSE: Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict the prognosis and treatment response. This study investigated whether circulating tumor cells (CTCs) detectable could reminder high risk of distant metastasis, provide prognostic information, and early indicate the response to the conventional therapy in patients with advanced NSCLC. PATIENTS AND METHODS: In this single-center prospective study, blood samples for CTC analysis were obtained from 59 patients with previously untreated, stage III or IV NSCLC both before and after administration of two cycles of chemotherapy...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28288939/breast-cancer-resistance-protein-bcrp-abcg2-and-p-glycoprotein-p-gp-abcb1-transport-afatinib-and-restrict-its-oral-availability-and-brain-accumulation
#8
Stéphanie van Hoppe, Rolf W Sparidans, Els Wagenaar, Jos H Beijnen, Alfred H Schinkel
Afatinib is a highly selective, irreversible inhibitor of EGFR and (HER)-2. It is orally administered for the treatment of patients with EGFR mutation-positive types of metastatic NSCLC. We investigated whether afatinib is a substrate for the multidrug efflux transporters ABCB1 and ABCG2 and whether these transporters influence oral availability and brain and other tissue accumulation of afatinib. We used in vitro transport assays to assess human (h)ABCB1-, hABCG2- or murine (m)Abcg2-mediated transport of afatinib...
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28288645/mesothelin-promotes-epithelial-to-mesenchymal-transition-and-tumorigenicity-of-human-lung-cancer-and-mesothelioma-cells
#9
Xiaoqing He, Liying Wang, Heimo Riedel, Kai Wang, Yong Yang, Cerasela Zoica Dinu, Yon Rojanasakul
BACKGROUND: Lung cancer and pleural mesothelioma are two of the most deadly forms of cancer. The prognosis of lung cancer and mesothelioma is extremely poor due to limited treatment modalities and lack of understanding of the disease mechanisms. We have identified mesothelin as a potentially unique therapeutic target that as a specific advantage appears nonessential in most cell types. Mesothelin (MSLN), a plasma membrane differentiation antigen, is expressed at a high level in many human solid tumors, including 70% of lung cancer and nearly all mesotheliomas...
March 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28285694/sbrt-for-oligoprogressive-oncogene-addicted-nsclc
#10
REVIEW
L Basler, S G C Kroeze, M Guckenberger
Lung cancer is one of the leading causes of cancer death in men and women and treatment outcome continues to lag behind other common cancer types. A subset of lung adenocarcinoma patients exhibit a somatic mutation in EGFR or an ALK rearrangement. In these patients, targeted TKI therapy results in higher response rates, improved PFS and reduced side effects compared with platinum-based chemotherapy. Despite initial activity of the TKIs, ultimately all patients present with disease progression after about a year on TKI therapy due to resistance development...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28285682/pretreatment-neutrophil-to-lymphocyte-ratio-as-a-marker-of-outcomes-in-nivolumab-treated-patients-with-advanced-non-small-cell-lung-cancer
#11
Stephen J Bagley, Shawn Kothari, Charu Aggarwal, Joshua M Bauml, Evan W Alley, Tracey L Evans, John A Kosteva, Christine A Ciunci, Peter E Gabriel, Jeffrey C Thompson, Susan Stonehouse-Lee, Victoria E Sherry, Elizabeth Gilbert, Beth Eaby-Sandy, Faith Mutale, Gloria DiLullo, Roger B Cohen, Anil Vachani, Corey J Langer
OBJECTIVES: Efficient use of nivolumab in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. In patients with metastatic melanoma treated with ipilimumab, a pretreatment neutrophil-to-lymphocyte ratio (NLR)<5 has been associated with improved survival. This retrospective cohort study aimed to determine whether the pretreatment NLR was associated with outcomes in NSCLC patients treated with nivolumab. METHODS: We reviewed the medical records of all patients with previously treated advanced NSCLC who received nivolumab between March 2015 and March 2016 outside of a clinical trial at the University of Pennsylvania...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28276856/safety-of-alectinib-for-the-treatment-of-metastatic-alk-rearranged-non-small-cell-lung-cancer
#12
Viola Zhu, S H Ou
Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) may derive significant clinical benefit from targeted therapies against this driver mutation, but progression is virtually inevitable. Alectinib is a next-generation ALK inhibitor that provides a novel treatment option for this group of patients. Areas covered: In this review, we summarize the overall safety and tolerability of alectinib. Specifically, we cover cardiovascular, gastrointestinal, hepatic, musculoskeletal, and respiratory adverse events...
March 3, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28275600/tyrosine-kinase-inhibitors-in-the-treatment-of-choroidal-metastases-from-non-small-cell-lung-cancer-a-case-report-and-review-of-literature
#13
Akshay Gopinathan Nair, Haresh T Asnani, Vinod C Mehta, Siddharth V Mehta, Rima S Pathak, Amit H Palkar, Indumati Gopinathan
BACKGROUND: Choroidal metastases being the sole presenting feature of lung cancer is rare. Erlotinib, a tyrosine kinase inhibitor (TKI), is used in the treatment of lung adenocarcinoma where tumor cells exhibit epidermal growth factor receptor (EGFR) mutations. We report a case of metastatic non-small-cell lung cancer (NSCLC) with choroidal metastasis, which was the sole presenting feature and which responded to erlotinib. METHODS: We performed a retrospective case review...
January 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/28274559/a-novel-technique-for-tumor-localization-and-targeted-lymphatic-mapping-in-early-stage-lung-cancer
#14
Krista J Hachey, Christopher S Digesu, Katherine W Armstrong, Denis M Gilmore, Onkar V Khullar, Brian Whang, Hisashi Tsukada, Yolonda L Colson
OBJECTIVE: To investigate safety and feasibility of navigational bronchoscopy (NB)-guided near-infrared (NIR) localization of small, ill-defined lung lesions and sentinel lymph nodes (SLN) for accurate staging in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with known or suspected stage I NSCLC were enrolled in a prospective pilot trial for lesion localization and SLN mapping via NB-guided NIR marking. Successful localization, SLN detection rates, histopathologic status of SLN versus overall nodes, and concordance to initial clinical stage were measured...
February 10, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28260630/development-and-validation-of-an-elisa-method-for-the-quantification-of-nivolumab-in-plasma-from-non-small-cell-lung-cancer-patients
#15
Alicja Puszkiel, Gaëlle Noé, Pascaline Boudou-Rouquette, Chloé Le- Cossec, Jennifer Arrondeau, Jean-Stephane Giraud, Audrey Thomas-Schoemann, Jérôme Alexandre, Michel Vidal, François Goldwasser, Benoit Blanchet
Nivolumab, an anti PD-1 monoclonal antibody, has been approved for the treatment of previously treated advanced or metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to develop and validate an ELISA method for the quantification of nivolumab in plasma from patients with NSCLC in order to perform future pharmacokinetic/pharmacodynamic (PK/PD) studies. A home-made ELISA was developed and validated according to the general recommendations for the immunoassays. Then, the ELISA method was applied to quantify plasma trough levels (Cmin) of nivolumab (3mg/kg every two weeks) in 27 NSCLC patients at days 14, 28 and 42 after start of treatment...
February 24, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28260402/cost-and-survival-analysis-before-and-after-implementation-of-dana-farber-clinical-pathways-for-patients-with-stage-iv-non-small-cell-lung-cancer
#16
David M Jackman, Yichen Zhang, Carole Dalby, Tom Nguyen, Julia Nagle, Christine A Lydon, Michael S Rabin, Kristen K McNiff, Belen Fraile, Joseph O Jacobson
PURPOSE: Increasing costs and medical complexity are significant challenges in modern oncology. We explored the use of clinical pathways to support clinical decision making and manage resources prospectively across our network. MATERIALS AND METHODS: We created customized lung cancer pathways and partnered with a commercial vendor to provide a Web-based platform for real-time decision support and post-treatment data aggregation. Dana-Farber Cancer Institute (DFCI) Pathways for non-small cell lung cancer (NSCLC) were introduced in January 2014...
March 4, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28260071/axl-and-met-receptor-tyrosine-kinases-are-essential-for-lung-cancer-metastasis
#17
Yun Jung Choi, Ji Hye Kim, Jin Kyung Rho, Joong Sun Kim, Chang-Min Choi, Woo Sung Kim, Jaekyoung Son, Jae Cheol Lee
The AXL and MET receptors regulate key processes in tumor growth, metastasis, and drug resistance; thus, they have recently been implicated as promising therapeutic targets in various tumors. We investigated the metastatic potential and crosstalk between these receptors in non‑small cell lung cancer (NSCLC). We found that the treatment of NSCLC cells with hepatocyte growth factor (HGF) and growth arrest-specific 6 (Gas6), as ligands for MET and AXL, respectively, promoted their migration and invasion ability...
March 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259951/sox2-inhibits-wnt-%C3%AE-catenin-signaling-and-metastatic-potency-of-cisplatin-resistant-lung-adenocarcinoma-cells
#18
Jinxi He, Juan Shi, Kangjian Zhang, Jing Xue, Jing Li, Jiali Yang, Juan Chen, Jun Wei, Hong Ren, Xiaoming Liu
Lung cancer remains one of the most common cancer-associated mortalities worldwide, and platinum-based doublet chemotherapies are recommended as the first‑line treatment for advanced non‑small cell lung cancer (NSCLC). However, the frequent development of multidrug resistance, to cisplatin regimens in particular, is a major cause of chemotherapy failure in patients with aggressive NSCLC. Wnt/β‑catenin signaling and sex‑determining region Y box 2 (Sox2) have been implicated in the development and progression and resistance to epidermal growth factor receptor‑targeting therapy in lung cancer...
February 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258962/renal-cell-carcinoma-with-pulmonary-metastasis-and-metachronous-non-small-cell-lung-cancer
#19
Isaac A Bowman, Ivan Pedrosa, Payal Kapur, James Brugarolas
INTRODUCTION: The development of a second primary malignancy in a patient with a preexisting diagnosis of metastatic cancer may be easily overlooked or misattributed to progression of disease. We report 3 patients with clear-cell renal cell carcinoma (RCC) metastatic to the lungs who were subsequently diagnosed with non-small-cell lung cancer (NSCLC). We examined the frequency of this occurrence within our institution and report on the radiographic findings that may help distinguish between metastatic RCC and primary lung cancers...
February 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28254730/management-of-brain-metastasized-non-small-cell-lung-cancer-nsclc-from-local-treatment-to-new-systemic-therapies
#20
REVIEW
G Tsakonas, L De Petris, S Ekman
Lung cancer has the highest frequency of brain dissemination compared to all other solid tumours. Classical treatment options such as brain irradiation have started to be questioned due to lack of survival benefit and risk for severe side effects. Oncogenic driven tumours have the highest frequency of brain dissemination among NSCLC patients and available targeted therapies have shown activity both intra-and extracranially, with an acceptable toxicity profile. The recent approval of immune checkpoint inhibitors for the treatment of NSCLC has complicated treatment selection even more...
March 2017: Cancer Treatment Reviews
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