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Targeted Oncology

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December 3, 2016: Targeted Oncology
Gillian M Keating
Afatinib (Giotrif(®), Gilotrif(®)) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. In the first-line treatment of patients with advanced lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations, afatinib significantly prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS), compared with gefitinib (LUX-Lung 7 trial). In the overall population of patients receiving first-line treatment for advanced lung adenocarcinoma with activating EGFR mutations, afatinib significantly prolonged PFS, but not OS, compared with pemetrexed plus cisplatin (LUX-Lung 3 trial) or gemcitabine plus cisplatin (LUX-Lung 6 trial)...
November 22, 2016: Targeted Oncology
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...
November 15, 2016: Targeted Oncology
Martin Chopra
No abstract text is available yet for this article.
November 4, 2016: Targeted Oncology
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...
October 27, 2016: Targeted Oncology
Vincent Yi-Fong Su, Chia-Jen Liu, Yuh-Min Chen, Teh-Ying Chou, Tzeng-Ji Chen, Sang-Hue Yen, Tzeon-Jye Chiou, Jin-Hwang Liu, Yu-Wen Hu
BACKGROUND: Currently, no large study addressing the relationship between lung cancer patients with different therapies and second primary malignancies (SPMs) is available. METHODS: Using the Taiwan National Health Insurance Research Database, we conducted a population-based cohort study. Patients with newly diagnosed lung cancer between 1997 and 2005 were enrolled and followed up until Dec. 31, 2011. The endpoint of the study was SPM occurrence. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort to that of the general population...
October 20, 2016: Targeted Oncology
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...
September 14, 2016: Targeted Oncology
Emma D Deeks
Ceritinib (Zykadia™) is an oral, selective inhibitor of the anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase which, after genetic rearrangement, acts as an oncogenic driver in a proportion of non-small cell lung cancers (NSCLCs). The drug is approved in several countries worldwide for the treatment of patients with ALK-positive, advanced NSCLC who have previously received the first-generation ALK inhibitor crizotinib (indication details may vary by country). Approval was based on its clinical benefit in this setting in the phase I and II trials known as ASCEND-1 and -2...
October 2016: Targeted Oncology
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)...
August 29, 2016: Targeted Oncology
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...
August 18, 2016: Targeted Oncology
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...
August 15, 2016: Targeted Oncology
Radoslaw Kwapiszewski, Sebastian D Pawlak, Karolina Adamkiewicz
The epidermal growth factor receptor (EGFR) is one of the most important and attractive targets for specific anticancer therapies. It is a robust regulator of pathways involved in cancer pathogenesis and progression. Thus far, clinical trials have demonstrated the benefits of monoclonal antibodies and synthetic tyrosine kinase inhibitors in targeting this receptor; however, novel strategies are still being developed. This article reviews the current state of efforts in targeting the EGFR in cancer therapy. Following a brief characterization of EGFR, we will present a complete list of anti-EGFR agents that are already approved, and available in clinical practice...
August 11, 2016: Targeted Oncology
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...
August 11, 2016: Targeted Oncology
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...
August 9, 2016: Targeted Oncology
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...
August 9, 2016: Targeted Oncology
Mario Scartozzi, Loic Vincent, Marielle Chiron, Stefano Cascinu
Colorectal cancer (CRC) is a leading tumour worldwide, and the median survival of metastatic patients with the latest therapeutic options today reaches 30 months. Therefore, it is important to plan a therapeutic strategy, able to optimize the use of the available drugs (fluoropyrimides, oxaliplatin, irinotecan and target biologic therapy), with the objective of maximizing the long-term efficacy, reducing toxicities and assuring better quality of life for the patients with mCRC. Among the most recently available drugs for the treatment of mCRC, aflibercept, a new antiangiogenetic agent, should be considered a promising therapeutical option for the second line setting...
August 2016: Targeted Oncology
Sandrine Faivre, Armand de Gramont, Eric Raymond
No abstract text is available yet for this article.
August 2016: Targeted Oncology
Jayaprakasam Madhumathi, Surapally Sridevi, Rama Shanker Verma
BACKGROUND: Human TNF-related apoptotic-inducing ligand (TRAIL) has been used successfully for targeted therapy of almost all cancers. Leukemia is the most common type of cancer in children, and despite the advances in therapeutic strategies, the survival rate in leukemia cases is very low. Overexpression of interleukin 2 receptor (IL2R) in hematological malignancies has been utilized to target leukemia. Here, we report an immunotoxin fusion construct of human IL2α and TRAIL for targeting leukemia...
August 2016: Targeted Oncology
Jeremy W Vandiver, Zachary Singer, Cara Harshberger
Anti-programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab are becoming increasingly important in the treatment of melanoma and non-small cell lung cancer. These agents are known to induce many immune-related adverse events, but rapid-onset nephritis and immune-related hyponatremia have not been described to date. We describe the case of an adult patient who developed severe hyponatremia and rapid-onset nephritis following the first infusion of nivolumab for metastatic melanoma.
August 2016: Targeted Oncology
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