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Current Cancer Drug Targets

Chenfei Zhou, Liangjun Zhu, Jun Ji, Fangmi Ding, Chao Wang, Qu Cai, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Nimotuzumab, a monoclonal antibody against EGFR, has been shown to be efficacious in the treatment of advanced pancreatic cancer, but its predictive marker has not been established. The present study was designed to investigate the impact of EGFR and KRAS status on the antitumor efficacy of nimotuzumab and to explore its underlying mechanism of action. EGFR expression levels of pancreatic cancer cell lines, BxPC3, Panc-1, and Patu-8988, were analyzed by Western blot and immunocytochemistry, and their KRAS status was determined by gene sequencing...
October 13, 2016: Current Cancer Drug Targets
Bhupinder Kumar, Rakesh Kumar, Ira-Ida Skvortsova, Vinod Kumar
A number of chemically diverse substances bind to the tubulin and inhibit cell proliferation by disrupting microtubule dynamics. There are four binding sites for the ligands binding to the tubulin; taxane/epothilone and laulimalide/peloruside binding ligands stabilize microtubule while vinca and colchicine binding site agents promote microtubule depolymerization. Most of the tubulin binding ligands disturb the tubulin-microtubule dynamic equilibrium but these may exhibit anticancer activities through different mechanisms...
September 28, 2016: Current Cancer Drug Targets
Na Fu, Hui Yao, Yuemin Nan, Liang Qiao
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Hepatitis C virus (HCV) infection is the predominant cause of chronic liver diseases and HCC, particularly in Western countries. Multiple molecular mechanisms are involved in the development and progression of HCV-related HCC, of which oxidative stress plays a pivotal role. HCV infection induces overproduction of reactive oxygen species (ROS) and impairs the function of endogenous antioxidants. Excessive amount of ROS directly damages DNA, lipids and proteins...
September 26, 2016: Current Cancer Drug Targets
Shi-Yan Yan, Jian-Gao Fan, Liang Qiao
Liver cancer is a common disease and the third leading cause of cancer-related deaths worldwide [1]. Hepatocellular carcinoma (HCC) is the most deadly form of liver cancer. Chronic hepatitis and subsequent liver fibrosis and cirrhosis are the major causes of HCC [2]. Chronic hepatitis B (CHB) is one of the most common infections worldwide. It is estimated that two billion people have been infected with hepatitis B virus (HBV), and up to 400,000 people worldwide are believed to have chronic HBV infection [3]...
September 26, 2016: Current Cancer Drug Targets
Ezequiel M Fuentes-Pananá, Abigail Morales-Sánchez
EBV-associated Gastric Cancer (EBVaGC) comprises about 9% of all cases of GC and constitutes a distinct clinicopathological and molecular entity. The pattern of viral expression in EBVaGC cannot be set to any of the previously EBV-associated malignancies. Several lines of evidence support that viral expression in EBVaGC is characterized by high transcription of the BamH1-A rightward transcript (BART), low-levels of EBNA-1 and lack of LMP1. The high transcription activity of the BamH1-A region is importantly directed to express BART miRNAs, supporting a critical role for these miRNAs during epithelial cell infection and carcinogenesis...
September 26, 2016: Current Cancer Drug Targets
Samantha Banford, David J Timson
UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important roles in vivo in the cell membrane. These are often involved in cell-cell adhesion, cytoskeleton regulation and immune recognition. pp-GalNAc-T6 has been shown to be upregulated in a number of types of cancer...
September 22, 2016: Current Cancer Drug Targets
Massimo Offidani, Silvia Gentili, Francesca Gay, Elena Aghemo, Laura Maracci, Laura Corvatta, Antonio Palumbo
High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients younger than 65 years of age with multiple myeloma (MM). However, this therapeutic approach has undergone substantial advances in this last decade, mainly due to the introduction of new drugs such as thalidomide, lenalidomide and bortezomib. These new drugs, in different combinations, have shown to significantly increase response rates after induction therapy and ASCT. Moreover, the positive results obtained with these agents in consolidation and maintenance strategies after ASCT strongly support the concept of continuous therapy, whose ultimate goal is the long-term control of the disease and the improvement of outcome...
September 19, 2016: Current Cancer Drug Targets
Uzma Malik, Aneela Javed
The human leucine-rich repeats and immunoglobulin like domains (LRIG) are evolutionary conserved family of single-pass transmembrane proteins. LRIG gene family includes three members, LRIG1 (formerly LIG1), LRIG2 and LRIG3, all of which are differentially expressed in human tissues and have long been proposed to be tumor suppressors. However, recently accumulated evidence on LRIG protein expression in human cancer appears to be inconsistent with this belief, as LRIG proteins have been found to be upregulated in certain tumors...
September 7, 2016: Current Cancer Drug Targets
Talha Shafi, Ishrat Jabeen
ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are major determinant of pharmacokinetic, safety and efficacy profiles of drugs thereby effluxing a broad range of endogenous substances across the plasma membrane. Overexpression of these transporters in various tumors is also implicated in the development of multidrug resistance (MDR) and thus, hampers the success of cancer chemotherapy. Modulators of these efflux transporters in combination with chemotherapeutics could be a promising concept to increase the effective intracellular concentration of anticancer drugs...
August 31, 2016: Current Cancer Drug Targets
Ilaria Giusti, Marianna Di Francesco, Vincenza Dolo
Glioblastoma is the most common and most malignant form of primary brain cancer and it is characterized by one of the highest mortality among human cancers. Maximal and aggressive surgical resection is the first approach treatment but it is not usually definitive, being the tumor characterized by a high proliferative rate and an extensive invasion. An early diagnosis, associated to a careful monitoring, is pivotal in glioblastoma treatment; the Magnetic Resonance Imaging is used for monitoring purpose, but it's not sensitive enough to detect very small tumors; a valid alternative could be a repeated biopsy, but it is associated to a significant morbidity: less invasive options for diagnosis and therapeutic monitoring are unfailingly researched...
August 13, 2016: Current Cancer Drug Targets
Francesca De Felice, Daniela Musio, Raffaele Cassese, Giovanni Luca Gravina, Vincenzo Tombolini
BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent brain tumor. Despite recent advances in treatment approaches the prognosis remains poor, with a median overall survival of 14.6 months. Immunotherapy is the subject of ongoing research and its benefit is becoming evident in other malignancies. Immune check-points such as cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed cell death receptor (PD-1) and indoleamine 2,3-dioxygenase (IDO) reduce immune response. OBJECTIVE: To clarify the role of immune check point inhibitors in GBM management...
August 13, 2016: Current Cancer Drug Targets
Rosa Luciano, Rossana Saracino, Giulia Battafarano, Antonio Perrotta, Melania Manco, Maurizio Muraca, Andrea Del Fattore, Michela Rossi
Glioblastoma multiforme represents one of the most aggressive tumor of central nervous system. Current therapy includes surgery, radiation and chemotherapy. These treatments are rarely curative and glioma are associated with a poor prognosis. Nanomedicine represents the most innovative branch of medicine since many studies demonstrated great advantage in the diagnosis and therapy of several diseases. In this review we will summarize the results obtained by the use of nanoparticles and extracellular vesicles in glioblastoma...
August 13, 2016: Current Cancer Drug Targets
Cinzia Dello Russo, Lucia Lisi, Lucio Tentori, Pierluigi Navarra, Grazia Graziani, Colin K Combs
Glioblastoma is the most common brain tumor in adults and is associated with a very low survival rate. The heterogeneity of the tumor microenvironment, its resistance to drug and radiation therapy, and its robust invasiveness all contribute to the poor outcome. Large numbers of glioma associated microglia and macrophages can accumulate within the tumor where they appear to have a role in prognosis. This has stimulated considerable interest in understanding the contribution of these cells to disease progression...
August 13, 2016: Current Cancer Drug Targets
Rutger Balvers, Clemens M F Dirven, Sieger Leenstra, Martine L M Lamfers
Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between patients. Both these phenomena are implicated in the variability in clinical outcome between patients, as well as the inevitable recurrence of these tumors after conventional treatment. The advent of selective cell culture protocols for the propagation of patient-derived glioma stem-like cells (GSCs) provides researchers the ability to selectively study the cells that could be at the root of tumor proliferation and resistance to therapy...
August 13, 2016: Current Cancer Drug Targets
Michele Dal Bo, Erika Tissino, Dania Benedetti, Chiara Caldana, Riccardo Bomben, Giovanni Del Poeta, Gianluca Gaidano, Francesca Maria Rossi, Pietro Bulian, Antonella Zucchetto, Valter Gattei
Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease characterized by the accumulation/expansion of a clonal population of neoplastic cells with the morphological appearance of small mature B lymphocytes in blood, bone marrow, and lymphoid organs. CD49d, the α chain of the α4β1 integrin heterodimer, is one of the main interactors between CLL cells and accessory cells in the microenvironmental sites and one of the main predictors of overall survival. In particular, CD49d is known to play a pivotal role in mediating both cell-cell and cell-matrix interactions in CLL-involved tissues eventually delivering prosurvival signals and protecting CLL cells from drug-induced damages...
August 9, 2016: Current Cancer Drug Targets
Hazem Ihsan Assi, Rita Assi
With increases in our understanding of the human genome and immune system, the treatment armamentarium for melanoma has benefitted from the development and approval of BRAF inhibitors, MEK inhibitors, immune checkpoint modulators via cytotoxic T-lymphocyte antigen-4 blockade, and PD-1 and PD-L1 inhibitors. These advances, however, have raised questions about combination therapy, the optimal sequential use of these agents, the limited assessment of response using traditional metrics, and the optimal selection of the population to be treated...
July 19, 2016: Current Cancer Drug Targets
Xinwei Geng, Xiaohui Wang, Dan Zhu, Songmin Ying
Silencing of two or more complementary signaling pathways can lead to cell death, while loss of any single genetic function does not show a severe phenotype thanks to backup solutions. This kind of interaction between two or more genes is coined 'synthetic lethality'. Since this was put forward in 1964, vast numbers of synthetic lethal interactions have been defined in yeast, and accumulating evidence suggests that some synthetic lethal interactions occur in humans. Synthetic lethality provides a new way to treat cancer, in which cancer cells can be targeted specifically...
July 5, 2016: Current Cancer Drug Targets
Qiaohua Zhu, Xinfa Yu, Zhi-Wei Zhou, Chengyu Zhou, Xiao-Wu Chen
BACKGROUND: To evaluate the proteomic response to alisertib (ALS) and identify the molecular targets of ALS in the treatment of hepatoblastoma, we examined the effect of ALS with a particular focus on the proliferation, cell cycle, autophagy, apoptosis, and chemosensitivity in HepG2 cells. MATERIALS AND METHODS: The stable-isotope labeling by amino acids in cell culture (SILAC) based quantitative proteomic approach was performed to evaluate the proteomic response to ALS...
June 30, 2016: Current Cancer Drug Targets
Alessandro Federico, Silvia Zappavigna, Marcello Dallio, Gabriella Misso, Francesco Merlino, Carmelina Loguercio, Ettore Novellino, Paolo X Paolo Grieco, Michele Caraglia
Urotensin II and Urotensin-II receptor are important molecular factors that regulate vasoconstriction and all the diseases that are linked to abnormalities in blood pressure regulation (i.e.: hypertension, kidney diseases, cirrhosis etc.). Recently Urotensin II and its receptor have also been involved in metabolic syndrome, diabetes and schizophrenia. Recent strong findings suggest thatUrotensin II and its receptor are involved in the onset and development of different epithelial cancers. Indeed, it was reported that cell growth, motility and invasion in human breast, bladder, prostate, colorectal and glioblastoma cancer cells were regulated by Urotensin II and Urotensin-II receptor axis...
June 20, 2016: Current Cancer Drug Targets
Cecilia Murphy, Jan Blanchard, Arnold Ganser, Eric Brown, John Hassell, R Keith Humpheries, Michael Morgan, Michael Heuser
Hematopoietic stem and progenitor cell differentiation is blocked in acute myeloid leukemia (AML) resulting in cytopenias and a high risk of death. Most patients with AML become resistant to treatment due to lack of effective cytotoxic and differentiation promoting compounds. High MN1 expression confers poor prognosis to AML patients and induces resistance to cytarabine and all-trans-retinoic acid (ATRA) induced differentiation. Using a high-throughput drug screening, we identified the dihydrofolate reductase (DHFR) antagonist pyrimethamine to be a potent inducer of apoptosis and differentiation in several murine and human leukemia cell lines...
June 16, 2016: Current Cancer Drug Targets
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