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Targeted Oncology

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https://www.readbyqxmd.com/read/29907952/bim-deletion-polymorphism-confers-resistance-to-osimertinib-in-egfr-t790m-lung-cancer-a-case-report-and-literature-review
#1
REVIEW
Xuanzong Li, Shijiang Wang, Butuo Li, Zhen Wang, Shuheng Shang, Yang Shao, Xindong Sun, Linlin Wang
The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib (AZD9291) has shown significant clinical efficacy against the EGFR T790M mutation in non-small cell lung cancer (NSCLC) patients. However, resistance inevitably occurs, and the mechanisms leading to treatment failure need to be further investigated. The B-cell lymphoma 2 (BCL-2)-like 11 (BIM) deletion polymorphism, which occurs at a frequency of 21% in East Asians but is absent in African and European populations, has been associated with resistance to first-generation EGFR TKIs, such as gefitinib and erlotinib; and is a poor prognostic factor for NSCLC patients with EGFR mutations...
June 16, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29882102/low-dose-continuous-5-fluorouracil-combined-with-leucovorin-nab-paclitaxel-oxaliplatin-and-bevacizumab-for-patients-with-advanced-pancreatic-cancer-a-retrospective-analysis
#2
William H Isacoff, Howard A Reber, Rudolph Bedford, William Hoos, Lola Rahib, Alexander Upfill-Brown, Timothy Donahue, O Joe Hines
BACKGROUND: Continuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic. OBJECTIVE: In this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy...
June 7, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29785577/atezolizumab-a-review-in-previously-treated-advanced-non-small-cell-lung-cancer
#3
REVIEW
Hannah A Blair
Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials...
May 21, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29785576/prognostic-impact-of-the-components-of-progressive-disease-on-survival-after-first-line-tyrosine-kinase-inhibitor-therapy-for-metastatic-renal-cell-carcinoma
#4
Takashi Ikeda, Hiroki Ishihara, Toshio Takagi, Tsunenori Kondo, Kazuhiko Yoshida, Junpei Iizuka, Kazunari Tanabe
BACKGROUND: According to the Response Evaluation Criteria in Solid Tumors (RECIST) classification, progressive disease (PD) is defined as target lesion growth (TLG), unequivocal non-target lesion growth (NTLG), or new lesion appearance (NLA). The prognostic impact of the components of PD in tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC) remains unknown. OBJECTIVE: We retrospectively evaluated the prognostic impact of these PD components on survival in patients with mRCC after first-line TKI therapy...
May 21, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29754184/discovery-of-a-potent-and-mutant-selective-egfr-inhibitor-that-overcomes-t790m-mediated-resistance-in-lung-cancer
#5
Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Young Hoon Sung, Woo Sung Kim, Sung-Eun Kim, Hyung Chul Ryu, Jae Sun Kim, Lu Guangying, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
BACKGROUND: Despite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now. OBJECTIVE: To determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR...
May 12, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29667105/the-role-of-autophagy-in-the-resistance-to-braf-inhibition-in-braf-mutated-melanoma
#6
Xiao Liu, Jinfeng Wu, Haihong Qin, Jinhua Xu
Malignant melanoma is the most aggressive and notorious skin cancer, and metastatic disease is associated with very poor long-term survival outcomes. Although metastatic melanoma patients with oncogenic mutations in the BRAF gene initially respond well to the treatment with specific BRAF inhibitors, most of them will eventually develop resistance to this targeted therapy. As a highly conserved catabolic process, autophagy is responsible for the maintenance of cellular homeostasis and cell survival, and is involved in multiple diseases, including cancer...
April 17, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29656320/the-role-of-mesothelin-as-a-diagnostic-and-therapeutic-target-in-pancreatic-ductal-adenocarcinoma-a-comprehensive-review
#7
Federico Nichetti, Antonio Marra, Francesca Corti, Alessandro Guidi, Alessandra Raimondi, Natalie Prinzi, Filippo de Braud, Sara Pusceddu
Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors...
April 14, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29644577/the-impact-of-dose-and-simultaneous-use-of-acid-reducing-agents-on-the-effectiveness-of-vemurafenib-in-metastatic-braf-v600-mutated-melanoma-a-retrospective-cohort-study
#8
Lotte M Knapen, Rutger H T Koornstra, Johanna H M Driessen, Bas van Vlijmen, Sander Croes, Stein Schalkwijk, Angela Colbers, Winald R Gerritsen, David M Burger, Frank de Vries, Nielka P van Erp
BACKGROUND: The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown. OBJECTIVES: To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs. PATIENT AND METHODS: A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012-March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital...
April 11, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29633072/association-of-expression-levels-or-activation-status-of-stat3-with-treatment-outcomes-of-sunitinib-in-patients-with-renal-cell-carcinoma
#9
Kazuhiro Yamamoto, Takuto Hara, Tsutomu Nakagawa, Midori Hirai, Hideaki Miyake, Masato Fujisawa, Ikuko Yano
BACKGROUND: The expression level of signal transducer and activator of transcription 3 (STAT3) in tumor cells is reported to associate with response to therapy and with survival time in various types of cancer. OBJECTIVE: This retrospective study aimed to elucidate the association of STAT3 expression in tumor cells with the therapeutic outcomes of sunitinib in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC who received sunitinib therapy were enrolled in this study...
April 9, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29623487/atezolizumab-in-metastatic-urothelial-carcinoma-outside-clinical-trials-focus-on-efficacy-safety-and-response-to-subsequent-therapies
#10
Pedro C Barata, Dhrmesh Gopalakrishnan, Vadim S Koshkin, Prateek Mendiratta, Matt Karafa, Kimberly Allman, Allison Martin, Jennifer Beach, Pam Profusek, Allison Tyler, Laura Wood, Moshe Ornstein, Timothy Gilligan, Brian I Rini, Jorge A Garcia, Petros Grivas
BACKGROUND: Little is known about the outcomes, safety, and response to subsequent therapies of patients with metastatic urothelial carcinoma (mUC) treated with atezolizumab outside clinical trials. OBJECTIVES: The objectives of the study include to report the clinical efficacy and safety of atezolizumab, and the response to future therapies in clinical practice outside clinical trials. PATIENT AND METHODS: This is a retrospective, single-center study including consecutive patients with confirmed mUC who received at least one dose of atezolizumab 1200 mg every 3 weeks between May 2016 and April 2017...
April 6, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29799096/avelumab-a-review-in-metastatic-merkel-cell-carcinoma
#11
REVIEW
Matt Shirley
Avelumab (Bavencio® ) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200...
June 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29700687/medical-treatment-options-for-patients-with-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-suffering-from-brain-metastases-and-or-leptomeningeal-disease
#12
Maximilian Hochmair
Brain metastases and/or leptomeningeal disease (LMD) with associated central nervous system (CNS) metastases are known complications of advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). It is important, therefore, to assess the activity of EGFR tyrosine kinase inhibitors (TKIs) versus such CNS complications. This review explores the literature reporting the intracranial activity of EGFR TKIs, and finds that there is evidence for varying efficacy of the approved agents, erlotinib, gefitinib, afatinib, and osimertinib in patients with CNS metastases...
June 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29582224/ramucirumab-as-second-line-therapy-in-metastatic-gastric-cancer-real-world-data-from-the-ramoss-study
#13
Maria Di Bartolomeo, Monica Niger, Giuseppe Tirino, Angelica Petrillo, Rosa Berenato, Maria Maddalena Laterza, Filippo Pietrantonio, Federica Morano, Maria Antista, Sara Lonardi, Lorenzo Fornaro, Stefano Tamberi, Elisa Giommoni, Alberto Zaniboni, Lorenza Rimassa, Gianluca Tomasello, Teodoro Sava, Massimiliano Spada, Tiziana Latiano, Alessandro Bittoni, Alessandro Bertolini, Ilaria Proserpio, Katia Bruna Bencardino, Francesco Graziano, Giordano Beretta, Salvatore Galdy, Jole Ventriglia, Simone Scagnoli, Andrea Spallanzani, Raffaella Longarini, Ferdinando De Vita
BACKGROUND: Ramucirumab-alone or combined with paclitaxel-represents one of the main options for patients failing first-line treatment for advanced gastric cancer. OBJECTIVE: The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the "real-life setting". PATIENTS AND METHODS: Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m2 i...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29492762/cabozantinib-versus-standard-of-care-comparators-in-the-treatment-of-advanced-metastatic-renal-cell-carcinoma-in-treatment-na%C3%A3-ve-patients-a-systematic-review-and-network-meta-analysis
#14
Elvira Schmidt, Johanna Lister, Monika Neumann, Witold Wiecek, Shuai Fu, Anne-Lise Vataire, Jelena Sostar, Shengnan Huang, Florence Marteau
BACKGROUND: Cabozantinib has recently been evaluated as a first-line treatment in advanced renal cell carcinoma (aRCC). OBJECTIVE: To indirectly assess efficacy of cabozantinib versus standard-of-care (SoC) comparators in the first-line treatment of aRCC. METHODS: We conducted a systematic literature review (SLR) to identify randomized controlled studies in the first-line setting for aRCC. The outcomes analyzed were overall survival (OS) and progression-free survival (PFS)...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29470785/the-abscopal-effect-in-the-era-of-cancer-immunotherapy-a-spontaneous-synergism-boosting-anti-tumor-immunity
#15
Zuzana Hlavata, Cinzia Solinas, Pushpamali De Silva, Michele Porcu, Luca Saba, Karen Willard-Gallo, Mario Scartozzi
Radiotherapy is one of the main treatment strategies used in cancer. Aside from the local control of the disease, which is mediated by a direct cytotoxic effect on tumor cells, radiotherapy has also been shown to exert immune-mediated local and systemic effects. Radiotherapy can elicit anti-tumor responses in distant sites from the radiation field; this phenomenon is known as the abscopal effect and has been described in patients previously treated with immune checkpoint blockade (ICB). Considering that the efficacy of immunotherapy has been demonstrated only in a subset of patients-who often benefit with lasting responses-efforts are ongoing to potentiate its activity with the development of new combination strategies...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29441438/combining-ibrutinib-with-chk1-inhibitors-synergistically-targets-mantle-cell-lymphoma-cell-lines
#16
Valentina Restelli, Monica Lupi, Micaela Vagni, Rosaria Chilà, Francesco Bertoni, Giovanna Damia, Laura Carrassa
BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with an unfavorable clinical course. Besides deregulation of the cell cycle, B cell receptor (BCR) signaling, essential for MCL proliferation and survival, is also often deregulated due to constitutive activation of Bruton's tyrosine kinase (BTK). The BTK inhibitor ibrutinib has been approved as a therapy for refractory MCL, and while it shows some clinical activity, patients frequently develop primary or secondary ibrutinib resistance and have very poor outcomes after relapsing following ibrutinib treatment...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29423595/alpha-emitters-and-targeted-alpha-therapy-in-oncology-from-basic-science-to-clinical-investigations
#17
Mehran Makvandi, Edouard Dupis, Jonathan W Engle, F Meiring Nortier, Michael E Fassbender, Sam Simon, Eva R Birnbaum, Robert W Atcher, Kevin D John, Olivier Rixe, Jeffrey P Norenberg
Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29423594/treatment-of-egfr-t790m-positive-non-small-cell-lung-cancer
#18
Joan Rou-En Choo, Chee-Seng Tan, Ross A Soo
The treatment of lung cancer has changed dramatically with the development of tyrosine kinase inhibitors (TKIs) that target sensitizing somatic mutations of the epidermal growth factor receptor (EGFR). Despite remarkable initial responses, patients eventually develop progressive disease, with the most common cause of resistance to first-line EGFR TKIs being the acquired T790M mutation. Various third-generation EGFR TKIs have been developed to specifically target this acquired mutation, of which osimertinib is currently the only approved agent...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29423593/tumor-hypoxia-as-an-enhancer-of-inflammation-mediated-metastasis-emerging-therapeutic-strategies
#19
Josh W DiGiacomo, Daniele M Gilkes
Metastasis is the leading cause of cancer-related deaths. Recent research has implicated tumor inflammation as a promoter of metastasis. Myeloid, lymphoid, and mesenchymal cells in the tumor microenvironment promote inflammatory signaling amongst each other and together with cancer cells to modulate sustained inflammation, which may enhance cancer invasiveness. Tumor hypoxia, a state of reduced available oxygen present in the majority of solid tumors, acts as a prognostic factor for a worse outcome and is known to have a role in tumor inflammation through the regulation of inflammatory mediator signals in both cancer and neighboring cells in the microenvironment...
April 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29404898/induction-chemotherapy-with-the-extreme-regimen-in-frail-patients-with-locally-advanced-head-and-neck-squamous-cell-carcinoma
#20
Valérie Cochin, Erwan de Mones, Laurence Digue, Muriel Garcia-Ramirez, Charles Dupin, Claire Majoufre, Philipe Fernandez, Amaury Daste
BACKGROUND: Induction chemotherapy (IC) with TPF (docetaxel, cisplatin, 5FU) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) is limited to fit patients. OBJECTIVE: We conducted a retrospective cohort study to assess the use of the EXTREME regimen (platinum-based therapy, 5FU, cetuximab) as IC in frail patients with LAHNSCC. PATIENTS AND METHODS: Retrospective analysis of all consecutive patients with unresectable LAHNSCC treated with the EXTREME regimen, with or without 5FU as IC, from two French centers from 2008 to 2015...
April 2018: Targeted Oncology
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