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- Volume 19, Issue 5, 2013
Current Pharmaceutical Design - Volume 19, Issue 5, 2013
Volume 19, Issue 5, 2013
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Targeting HER Receptors in Cancer
Authors: Alberto Ocana and Atanasio PandiellaReceptor tyrosine kinases play important roles in animal development and their deregulation has been linked to several pathologies, including cancer or diabetes. In cancer, the ERBB/HER family of receptors has been shown to participate in the pathophysiology of breast, gastric, colorectal, lung and head and neck tumors. Activation of HER receptors occurs by receptor-receptor interactions facilitated by ligand binding, overe Read More
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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Current Status and Future Perspectives in the Development of Novel Irreversible Inhibitors for the Treatment of Mutant Non-small Cell Lung Cancer
Conventional chemotherapeutic regimens have reached an efficacy plateau against most solid tumors and deal with significant toxicity. Recently, the goal of oncologic research to improve outcome and reduce treatment-related side-effects has led to the development of novel anticancer treatments targeting specific proteins or genes involved in cancer growth and progression. In particular, the tyrosine- kinase inhibitors ( Read More
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Detection and Therapeutic Implications of c-Met Mutations in Small Cell Lung Cancer and Neuroendocrine Tumors
Authors: J. Voortman, T. Harada, R.P. Chang, J.K. Killian, M. Suuriniemi, W.I. Smith, P.S. Meltzer, M. Lucchi, Y. Wang and G. GiacconeBackground. We evaluated the mutation status of c-Met in small cell lung cancer (SCLC) and neuroendocrine tumors (NET), for which relatively limited therapeutic targets have been explored. Materials and Methods. c-Met was re-sequenced using cell lines and clinical samples. For in vitro studies, DNA constructs containing a juxtamembrane domain (JMD) and tyrosine kinase domain (TKD) were generated. Detected mutati Read More
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Anti-metastatic Treatment in Colorectal Cancer: Targeting Signaling Pathways
Authors: Clara Lemos, Ulrike Sack, Felicitas Schmid, Manisha Juneja and Ulrike SteinColorectal cancer is one of the most common cancers worldwide and one of the leading causes of cancer-related death in the Western world. Tumor progression towards metastasis affects a large number of patients with colorectal cancer and seriously affects their clinical outcome. Therefore, considerable effort has been made towards the development of therapeutic strategies that can decrease or prevent colorect Read More
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Inhibition of RET Activated Pathways: Novel Strategies for Therapeutic Intervention in Human Cancers
Authors: Libero Santarpia and Giulia BottaiThe REarranged during Transfection (RET) proto-oncogene and its activated signalling pathways have been shown to play an important role in cancer. RET genetic alterations including germline, somatic mutations and gene rearrangements have been demonstrated in several solid tumours, and numerous clinical trials using multikinase inhibitors containing RET as a target have shown significant activity against RET. Sorafenib Read More
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Modulation of Sensitivity to Antitumor Agents by Targeting the MAPK Survival Pathway
Authors: Giacomo Cossa, Laura Gatti, Giuliana Cassinelli, Cinzia Lanzi, Nadia Zaffaroni and Paola PeregoMitogen-activated protein kinases (MAPK) are involved in a complex network which regulates a variety of cellular processes including proliferation, survival and death. The molecular characterization of the pathway has shown aberrant activation in several human tumors, due to the deregulation of receptor tyrosine kinases or to mutations of pathway components. Progress in understanding the MAPK network has led to the develo Read More
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PI3K Pathway Inhibitors: Better Not Left Alone
Authors: Ben Markman, Jessica J. Tao and Maurizio ScaltritiThe PI3K/Akt/mTOR signaling pathway plays a key role in diverse physiologic processes. It is also central to many aspects of the malignant process. Genetic phenomena that lead to constitutive pathway activation are common in human cancer; the most relevant are mutations affecting the catalytic subunit of PI3K and loss of function of the PTEN tumor suppressor. These factors have made this important cascade attractive Read More
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The Intriguing Interplay Between Therapies Targeting the Epidermal Growth Factor Receptor, the Hypoxic Microenvironment and Hypoxia-inducible Factors
Despite their individual key roles in promoting cancer progression and treatment resistance, our knowledge about the impact of tumor hypoxia on the activity of the epidermal growth factor receptor (EGFR) pathway in cancer and vice versa remains limited. Preclinical and clinical studies support an important link between hypoxia and upregulation of EGFR in cancers that do not display genetic alterations of the receptor. S Read More
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Synergistic Antiproliferative and Antiangiogenic Effects of EGFR and mTOR Inhibitors
Authors: L. Porcelli, A.E. Quatrale, P. Mantuano, N. Silvestris, J.F. Rolland, L. Biancolillo, A. Paradiso and A. AzzaritiSingle-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, mainly because escape or resistance mechanisms are activated once a signalling molecule is inhibited. Rational combinations of target-specific agents could counteract this response providing a useful strategy in cancer treatment. In this regard, the EGFR and mTOR inhibitors have been used together to generate a sy Read More
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Molecular Mechanisms and Modulation of Key Pathways Underlying the Synergistic Interaction of Sorafenib with Erlotinib in Non-Small-Cell-Lung Cancer (NSCLC) Cells
Authors: E. Giovannetti, M. Labots, H. Dekker, E. Galvani, J.S.W. Lind, R. Sciarrillo, R. Honeywell, E.F. Smit, H.M. Verheul and G.J. PetersCombination of drugs with different targets is a logical approach to overcome multilevel cross-stimulation among key pathways in NSCLC progression such as EGFR, K-Ras and VEGFR. The sorafenib-erlotinib combination showed clinical activity and acceptable safety. Therefore, we evaluated mechanisms underlying sorafenib-erlotinib interaction in seven NSCLC cell lines selected for their heterogeneous pattern of E Read More
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Enhancement of the Antiproliferative Activity of Gemcitabine by Modulation of c-Met Pathway in Pancreatic Cancer
Pancreatic-ductal-adenocarcinoma (PDAC) is amongst the most lethal malignancies, mainly because of its metastatic spread and multifactorial chemoresistance. Since c-Met is a marker of pancreatic-cancer-stem-cells (CSC), playing a key role in metastasis and chemoresistance, this study evaluated the therapeutic potential of the novel c-Met/ALK inhibitor crizotinib against PDAC cells, including the Capan-1-gemcitabine-resi Read More
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Targeting the Akt-pathway to Improve Radiosensitivity in Glioblastoma
Glioblastoma multiforme (GMB) is the most malignant and common type of all astrocytic tumors. Current standard of care entails maximum surgical resection of the tumor, followed by radiotherapy and chemotherapy, usually by the alkylating agent Temozolomide (TMZ). Despite this aggressive combination therapy, the survival rate of GBM patients is still low. Deregulation of the phosphatidylinositol 3-kinase (PI3K) / A Read More
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Irinotecan Resistance is Accompanied by Upregulation of EGFR and Src Signaling in Human Cancer Models
Authors: Amelie Petitprez and Annette K. LarsenIrinotecan is a major drug for treatment of metastatic colorectal cancer and a promising agent for other applications like gastric cancer. Its clinical activity is currently limited by both intrinsic (natural) and acquired drug resistance. A better understanding of the underlying resistance mechanisms is needed to develop novel therapeutic strategies. Exposure of tumor cells to irinotecan or its active metabolite SN-38 is accompanied b Read More
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Volumes & issues
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Volume 31 (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
- Issue 42
- Issue 41
- Issue 40
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- Issue 31
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- Issue 27
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- Issue 19
- Issue 18
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- Issue 16
- Issue 15
- Issue 28
- Issue 14
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- Issue 12
- Issue 11
- Issue 10
- Issue 9
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- Issue 6
- Issue 5
- Issue 4
- Issue 3
- Issue 2
- Issue 1
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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