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Targeted Oncology

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https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#1
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28138797/exploiting-micrornas-as-cancer-therapeutics
#2
Tamsin Robb, Glen Reid, Cherie Blenkiron
miRNAs are a well-studied class of non-coding RNAs, predominantly functioning to down-regulate gene expression from messenger RNA (mRNA) in a targeted manner by binding to complementary sequence on the target mRNA. Many miRNAs have been linked to the development of hallmarks of cancer. miRNAs represent valuable therapeutic targets to exploit in the search for novel cancer treatments, due to their ubiquitous expression and their ability to tightly regulate the gene expression of a whole host of genes and pathways in a single hit...
January 30, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28120215/erratum-to-a-combination-of-the-telomerase-inhibitor-bibr1532-and-paclitaxel-synergistically-inhibit-cell-proliferation-in-breast-cancer-cell-lines
#3
Yi Shi, Lin Sun, Ge Chen, Dongyan Zheng, Li Li, Wanguo Wei
No abstract text is available yet for this article.
January 24, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28110417/splenic-enlargement-and-bone-marrow-hyperplasia-in-patients-receiving-trastuzumab-emtansine-for-metastatic-breast-cancer
#4
Michael Kosmin, Andreas Makris, Noorulhuda Jawad, David Woolf, David Miles, Anwar R Padhani
BACKGROUND: An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations. OBJECTIVE: To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer...
January 21, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28084572/clinical-implications-of-cytotoxic-t-lymphocyte-antigen-4-expression-on-tumor-cells-and-tumor-infiltrating-lymphocytes-in-extrahepatic-bile-duct-cancer-patients-undergoing-surgery-plus-adjuvant-chemoradiotherapy
#5
Yu Jin Lim, Jaemoon Koh, Kyubo Kim, Eui Kyu Chie, Sehui Kim, Kyoung Bun Lee, Jin-Young Jang, Sun Whe Kim, Do-Youn Oh, Yung-Jue Bang
BACKGROUND: There currently is only limited knowledge on the role of tumor-specific immunity in cholangiocarcinoma. OBJECTIVE: This study evaluated the clinical implications of cytotoxic T lymphocyte antigen-4 (CTLA-4) expression levels and CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) in extrahepatic bile duct (EHBD) cancer. PATIENTS AND METHODS: Immunohistochemistry of CTLA-4, CD4, and CD8 was performed for 77 EHBD cancer patients undergoing surgery plus adjuvant chemoradiotherapy...
January 13, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27995439/immuno-oncology-the-third-paradigm-in-early-drug-development
#6
Juan Martin-Liberal, Cinta Hierro, Maria Ochoa de Olza, Jordi Rodon
Clinical researchers in oncology face the difficulty of developing new drugs for treating cancer patients. This challenge nowadays extends towards new horizons since a high number of drugs are developed in each of the three paradigms: classical cytotoxics, new targeted agents, and emergent immunotherapeutic approaches. Over the last decade, there has been an unstoppable progress in this third paradigm, to the extent that in 2013 immunotherapy was granted the scientific breakthrough of the year. However, the novel mechanisms of action of these immunotherapeutic agents entail a whole new series of concepts, resulting in a number of unresolved questions to which clarification is crucial for their success: establishment of accurate preclinical models able to predict human toxicities, better selection of candidate populations, finding and validation of predictive biomarkers, definition of suitable endpoints, improvements in first-in-human study designs, proposal of more accurate radiological response criteria, management of novel immune-related toxicities and development of combinations based on a biological rationale...
December 20, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27943153/phase-i-ii-randomized-trial-of-sorafenib-and-bevacizumab-as-first-line-therapy-in-patients-with-locally-advanced-or-metastatic-hepatocellular-carcinoma-north-central-cancer-treatment-group-trial-n0745-alliance
#7
Joleen M Hubbard, Michelle R Mahoney, William S Loui, Lewis R Roberts, Thomas C Smyrk, Zoran Gatalica, Mitesh Borad, Shaji Kumar, Steven R Alberts
BACKGROUND: Angiogenesis has been a major target of novel drug development in hepatocellular carcinoma (HCC). It is hypothesized that the combination of two antiangiogenic agents, sorafenib and bevacizumab, will provide greater blockade of angiogenesis. OBJECTIVE: To determine the optimal dose, safety, and effectiveness of dual anti-angiogenic therapy with sorafenib and bevacizumab in patients with advanced HCC. PATIENTS AND METHODS: Patients with locally advanced or metastatic HCC not amenable for surgery or liver transplant were eligible...
December 9, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/28000147/erratum-to-aflibercept-a-new-way-to-target-angiogenesis-in-the-second-line-treatment-of-metastatic-colorectal-cancer-mcrc
#8
Mario Scartozzi, Loic Vincent, Marielle Chiron, Stefano Cascinu
No abstract text is available yet for this article.
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27981431/adjusting-overall-survival-estimates-after-treatment-switching-a-case-study-in-metastatic-castration-resistant-prostate-cancer
#9
Konstantina Skaltsa, Cristina Ivanescu, Shevani Naidoo, De Phung, Stefan Holmstrom, Nicholas R Latimer
BACKGROUND: If patients in oncology trials receive subsequent therapy, standard intention-to-treat (ITT) analyses may inaccurately estimate the overall survival (OS) effect of the investigational product. In this context, a post-hoc analysis of the phase 3 PREVAIL study was performed with the aim to compare enzalutamide with placebo in terms of OS, adjusting for potential confounding from switching to antineoplastic therapies that are not part of standard metastatic castration-resistant prostate cancer (mCRPC) treatment pathways in some jurisdictions...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27975152/phase-i-ii-study-of-refametinib-bay-86-9766-in-combination-with-gemcitabine-in-advanced-pancreatic-cancer
#10
Jean-Luc Van Laethem, Hanno Riess, Jacek Jassem, Michael Haas, Uwe M Martens, Colin Weekes, Marc Peeters, Paul Ross, John Bridgewater, Bohuslav Melichar, Stefano Cascinu, Piotr Saramak, Patrick Michl, David Van Brummelen, Alberto Zaniboni, Wollf Schmiegel, Svein Dueland, Marius Giurescu, Vittorio L Garosi, Katrin Roth, Anke Schulz, Henrik Seidel, Prabhu Rajagopalan, Michael Teufel, Barrett H Childs
BACKGROUND: Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer. METHODS: Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27844272/resistance-to-targeted-therapies-in-renal-cancer-the-importance-of-changing-the-mechanism-of-action
#11
I Duran, J Lambea, P Maroto, J L González-Larriba, Luis Flores, S Granados-Principal, M Graupera, B Sáez, A Vivancos, O Casanovas
Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27796762/new-biomarkers-for-selecting-the-best-therapy-regimens-in-metastatic-castration-resistant-prostate-cancer
#12
Isabel Heidegger, Axel Heidenreich, David Pfister
Prostate cancer is the most common cancer in men. In recent years, several new targeted therapeutic agents for the treatment of metastatic castration resistant prostate cancer (mCRPC) have been developed. These include androgen receptor targeting agents, new taxanes, radium-223, and immunotherapies. In this short review, we provide a summary of clinical and preclinical biomarkers for each of these new treatment strategies, also including new markers currently presented in conference papers only. Moreover, we address the role of these biomarkers in clinical routine with the aim to select best-personalized treatment strategies for patients...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27638381/regorafenib-in-the-real-life-clinical-practice-data-from-the-czech-registry
#13
Katerina Kopeckova, Tomas Buchler, Zbynek Bortlicek, Karel Hejduk, Renata Chloupkova, Bohuslav Melichar, Petra Pokorna, Jiri Tomasek, Zdenek Linke, Lubos Petruzelka, Igor Kiss, Jana Prausova
OBJECTIVE: To describe the use of regorafenib for the treatment of metastatic colorectal cancer (mCRC) in clinical practice in the Czech Republic, and to describe the clinical outcomes of patients in terms of safety and survival. PATIENTS AND METHODS: The data of patients treated with regorafenib were extracted from the national CORECT registry. The CORECT registry is a non-interventional post-marketing database, gathering information about patients with CRC and treated with targeted agents...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27573024/the-unexpected-roles-of-aurora-a-kinase-in-gliobastoma-recurrences
#14
Estelle Willems, Arnaud Lombard, Matthias Dedobbeleer, Nicolas Goffart, Bernard Rogister
The main obstacle for the cure of glioblastoma (GBM) is systematic tumor recurrence after treatment. More than 90 % of GBM tumors are indeed recurrent within 5 years after diagnosis and treatment. We urgently need new therapies to specifically address these deadly relapses. A major advance in the understanding of GBM recurrence is the identification of GBM-Initiating Cells (GIC), characterized by their abilities for self-renewal, multilineage differentiation, and proliferation. It appears that these features of GIC could be modulated by the mitotic kinase Aurora A (AurA)...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27538584/response-to-tyrosine-kinase-inhibitors-in-lung-adenocarcinoma-with-the-rare-epidermal-growth-factor-receptor-mutation-s768i-a-retrospective-analysis-and-literature-review
#15
Xiaoli Zhu, Qianming Bai, Yongming Lu, Peng Qi, Jianhui Ding, Jialei Wang, Xiaoyan Zhou
BACKGROUND: The rare epidermal growth factor receptor (EGFR) mutation S768I has only been reported sporadically in patients with lung adenocarcinoma (AC). OBJECTIVE: This study aimed to investigate the prevalence of the S768I mutation in Chinese patients with lung AC and to retrospectively analyze the response of S768I mutants to tyrosine kinase inhibitors (TKIs). PATIENTS AND METHODS: A total of 6698 tissue specimens of lung AC were collected from the Department of Pathology of Shanghai Cancer Center of Fudan University between 2013 and 2015 and screened for EGFR mutations...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27526062/effect-of-targeting-clusterin-using-ogx-011-on-antitumor-activity-of-temsirolimus-in-a-human-renal-cell-carcinoma-model
#16
Masatomo Nishikawa, Hideaki Miyake, Martin Gleave, Masato Fujisawa
BACKGROUND: It has not been well documented that the modulation of stress response mediates the efficacy of the mammalian target of rapamycin (mTOR) inhibitor in renal cell carcinoma (RCC). OBJECTIVE: The objective of this study was to investigate whether the activity of the mTOR inhibitor temsirolimus against RCC could be enhanced by OGX-011, an antisense oligodeoxynucleotide (ODN) targeting the stress-activated chaperone clusterin. METHODS: We investigated the efficacy of combined treatment with temsirolimus plus OGX-011 in a human RCC Caki-1 model focusing on the effects on apoptotic and autophagic pathways...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27510230/targeting-multiple-oncogenic-pathways-for-the-treatment-of-hepatocellular-carcinoma
#17
Supritha G Swamy, Vivek H Kameshwar, Priya B Shubha, Chung Yeng Looi, Muthu K Shanmugam, Frank Arfuso, Arunasalam Dharmarajan, Gautam Sethi, Nanjunda Swamy Shivananju, Anupam Bishayee
Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer diagnosed worldwide. HCC occurs due to chronic liver disease and is often diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are currently used as first-line agents for HCC therapy, but these are non-selective cytotoxic molecules with significant side effects. Sorafenib, a multi-targeted tyrosine kinase inhibitor, is the only approved targeted drug for HCC patients. However, due to adverse side effects and limited efficacy, there is a need for the identification of novel pharmacological drugs beyond sorafenib...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27503006/impact-of-diabetes-on-outcomes-of-sorafenib-therapy-for-hepatocellular-carcinoma
#18
Giovan Giuseppe Di Costanzo, Raffaella Tortora, Filomena Morisco, Luigi Addario, Maria Guarino, Gabriella Cordone, Luigia Falco, Nicola Caporaso
BACKGROUND: Patients with diabetes are at increased risk of developing hepatocellular carcinoma (HCC) and have a poorer prognosis as compared to non-diabetics when HCC occurs. Diabetics with non-HCC cancers are at higher risk of toxicity related to systemic therapy, but data on HCC are lacking. OBJECTIVE: The aim of this study was to evaluate safety and effectiveness of sorafenib in HCC patients according to the presence/absence of diabetes. PATIENTS AND METHODS: From October 2008 to June 2014, 313 patients with HCC treated with sorafenib were enrolled...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27503005/mtor-inhibitors-in-castration-resistant-prostate-cancer-a-systematic-review
#19
REVIEW
Cara M Statz, Sara E Patterson, Susan M Mockus
BACKGROUND: The progression of prostate cancer to castration-resistant prostate cancer (CRPC) is often a result of somatic alterations in the PI3K/Akt/mTOR (mammalian target of rapamycin) pathway, suggesting that therapies targeting this pathway might lead to improved survival and efficacy. Here, we systematically evaluate the results of clinical trials investigating mTOR inhibition in CRPC and utilize preclinical data to predict clinical outcomes. METHODS: Trials included in the study were identified through PubMed and via review of conference abstracts cited by relevant review articles...
February 2017: Targeted Oncology
https://www.readbyqxmd.com/read/27924459/patient-reported-outcomes-and-quality-of-life-with-sunitinib-versus-placebo-for-pancreatic-neuroendocrine-tumors-results-from-an-international-phase-iii-trial
#20
Aaron Vinik, Andrew Bottomley, Beata Korytowsky, Yung-Jue Bang, Jean-Luc Raoul, Juan W Valle, Peter Metrakos, Dieter Hörsch, Rajiv Mundayat, Arlene Reisman, Zhixiao Wang, Richard C Chao, Eric Raymond
OBJECTIVE: The objective of this analysis was to compare patient-reported outcomes and health-related quality of life (HRQoL) in a pivotal phase III trial of sunitinib versus placebo in patients with progressive, well-differentiated pancreatic neuroendocrine tumors (NCT00428597). PATIENTS AND METHODS: Patients received sunitinib 37.5 mg (n = 86) or placebo (n = 85) on a continuous daily-dosing schedule until disease progression, unacceptable adverse events (AEs), or death...
December 2016: Targeted Oncology
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