E2F1 and NF- κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets.
E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets. Curr Cancer Drug Targets. 2016;16(9):765-772 Authors: Huang Y, Chen R, Zhou J Abstract Inflammation is the fundamental protective response; however disordered immuno-response can cause chronic human disease, including cancer. Inflammatory cells and mediators are essential to the tumor microenvironment and dissection of this complex molecular and cellular milieu may elucidate a connection between cancer and inflammation and help to identify potential novel therapeutic targets. Thus, focusing on tra...
Source: Current Cancer Drug Targets - October 25, 2016 Category: Cancer & Oncology Authors: Huang Y, Chen R, Zhou J Tags: Curr Cancer Drug Targets Source Type: research

Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as Well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde.
Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as Well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde. Curr Cancer Drug Targets. 2016;16(9):796-806 Authors: Chen TW, Tsai KD, Yang SM, Wong HY, Liu YH, Cherng J, Chou KS, Wang YT, Cuizon J, Cherng JM Abstract Cinnamomum verum is used to make the spice cinnamon and has been used for more than 5000 years by both of the two most ancient forms of medicine in the words: Ayurveda and traditional Chinese herbal medicines for various applications suc...
Source: Current Cancer Drug Targets - October 25, 2016 Category: Cancer & Oncology Authors: Chen TW, Tsai KD, Yang SM, Wong HY, Liu YH, Cherng J, Chou KS, Wang YT, Cuizon J, Cherng JM Tags: Curr Cancer Drug Targets Source Type: research

Pyrimethamine as a Potent and Selective Inhibitor of Acute Myeloid Leukemia Identified by High-throughput Drug Screening.
r M Abstract Hematopoietic stem and progenitor cell differentiation are 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 alltrans-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 se...
Source: Current Cancer Drug Targets - October 25, 2016 Category: Cancer & Oncology Authors: Sharma A, Jyotsana N, Lai CK, Chaturvedi A, Gabdoulline R, Görlich K, Murphy C, Blanchard JE, Ganser A, Brown E, Hassell JA, Humphries RK, Morgan M, Heuser M Tags: Curr Cancer Drug Targets Source Type: research

Refractory Chronic Lymphocytic Leukemia: A Therapeutic Challenge.
Abstract Despite impressive therapeutic progress represented by the advent of chemoimmunotherapy, chronic lymphocytic leukemia (CLL) remains incurable by conventional modalities. Refractory CLL defined by non-response to treatment or relapse/progression within 6 months is associated with multiple unfavourable prognostic factors such as p53 pathway disruption, deteriorating patient condition, increased risk of severe infections, and poor response to treatment, resulting in a very short overall survival. Therefore, refractory CLL represents a highly challenging situation for the hematologist as well as the patient. ...
Source: Current Cancer Drug Targets - October 22, 2016 Category: Cancer & Oncology Authors: Smolej L Tags: Curr Cancer Drug Targets Source Type: research

Therapeutic Approach to Patients with Chronic Lymphocytic Leukemia and Significant Comorbid Conditions.
Abstract Clinical trials in chronic lymphocytic leukemia (CLL) have focused mainly on younger fit patients until recently. However, CLL is a disease of elderly and many patients have significant comorbid conditions which together with advanced age preclude the use of aggressive regimens like FCR (fludarabine, cyclophosphamide, rituximab). Therefore, parameters such as performance status, renal function and number/severity of comorbidities together with clinical judgment should be used to guide the decision-making process regarding intensity of treatment. Two large randomized trials recently demonstrated that addit...
Source: Current Cancer Drug Targets - October 22, 2016 Category: Cancer & Oncology Authors: Smolej L Tags: Curr Cancer Drug Targets Source Type: research

Mechanistic and Clinical Aspects of Lenalidomide Treatment for Chronic Lymphocytic Leukemia.
Abstract There have been significant advances in our understanding of the pathogenesis of chronic lymphocytic leukemia (CLL) over the last decade, which has been accompanied by a rapid increase in treatment options. Inhibitors of BCRsignaling such as ibrutinib and idelalisib, and pro-apoptotic agents such as ABT- 199 have shown great promise in initial clinical trials and have been at the forefront of recent developments. However, despite the encouraging early data, these agents do not appear to represent a "cure" for CLL and mechanisms of resistance to these agents have already been identified. In light...
Source: Current Cancer Drug Targets - October 22, 2016 Category: Cancer & Oncology Authors: Riches JC, Gribben JG Tags: Curr Cancer Drug Targets Source Type: research

Targeting Signaling Pathways in Chronic Lymphocytic Leukemia.
Abstract Various signal transduction pathways have been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), which is characterized by the progressive accumulation of monoclonal CD5+ B cells in the blood. B cell receptor (BCR) signaling appears to have a crucial role in disease onset and is thought to be induced by self or non-self-antigen recognition leading to chronic stimulation. Several of the kinases functioning downstream of the BCR are aberrantly expressed or constitutively activated in CLL. Yet, these kinases have additional roles, particularly in chemokine receptor signaling, which is ess...
Source: Current Cancer Drug Targets - October 22, 2016 Category: Cancer & Oncology Authors: Muggen AF, Singh SP, Hendriks RW, Langerak AW Tags: Curr Cancer Drug Targets Source Type: research

Deregulation of Apoptosis - Is it Still an Important Issue in Pathogenesis of Chronic Lymphocytic Leukemia?
Abstract Chronic lymphocytic leukemia (CLL), a clonal expansion of B CD5+ cells, is the most common type of adult leukemia in western countries. The accumulation of neoplastic B-cells is primarily caused by prolonged life-span of these cells due to deregulation of apoptosis, and only marginally due to a higher proliferation rate. In spite of numerous reports characterizing particular mechanisms of B-CLL cell apoptosis, still relatively little is known about the complex regulation of this process. Therefore, more detailed research is required to understand the complicated mechanisms and regulatory processes of apop...
Source: Current Cancer Drug Targets - October 22, 2016 Category: Cancer & Oncology Authors: Podhorecka M, Macheta A, Bozko M, Bozko A, Malek NP, Bozko P Tags: Curr Cancer Drug Targets Source Type: research

Functional and Clinical Significance of the Integrin Alpha Chain CD49d Expression in Chronic Lymphocytic Leukemia.
Abstract 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-invo...
Source: Current Cancer Drug Targets - October 22, 2016 Category: Cancer & Oncology Authors: Dal Bo M, Tissino E, Benedetti D, Caldana C, Bomben R, Poeta GD, Gaidano G, Rossi FM, Bulian P, Zucchetto A, Gattei V Tags: Curr Cancer Drug Targets Source Type: research

Editorial (Thematic Issue: Pathogenetic Mechanisms of CLL - A Target in Therapy).
PMID: 27758697 [PubMed - in process] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - October 22, 2016 Category: Cancer & Oncology Authors: Bozko M, Podhorecka M, Macheta A, Bozko A, Malek NP, Bozko P Tags: Curr Cancer Drug Targets Source Type: research

EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab treatment in vivo.
Abstract 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. Anti-tumor effect of nimotuzumab on the cell lines were eva...
Source: Current Cancer Drug Targets - October 13, 2016 Category: Cancer & Oncology Authors: Zhou C, Zhu L, Ji J, Ding F, Wang C, Cai Q, Yu Y, Zhu Z, Zhang J Tags: Curr Cancer Drug Targets Source Type: research

Epstein-Barr Virus-associated Gastric Cancer and Potential Mechanisms of Oncogenesis.
ute;nchez A Abstract 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 epi...
Source: Current Cancer Drug Targets - September 26, 2016 Category: Cancer & Oncology Authors: Fuentes-Pananá EM, Morales-Sánchez A Tags: Curr Cancer Drug Targets Source Type: research

Hepatitis B virus (HBV) infection and hepatocellular carcinoma- New insights for an old topic.
This article discusses the importance and approaches for HCC screening in HBV-infected individuals, the risk factors of HCC, the possible mechanisms leading to HCC and the potential therapeutic approaches of HBV-related HCC. PMID: 27677954 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - September 26, 2016 Category: Cancer & Oncology Authors: Liang Q, Yan SY, Jian-Gao F Tags: Curr Cancer Drug Targets Source Type: research

Role of oxidative stress in Hepatitis C Virus induced hepatocellular carcinoma.
Abstract 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. Meanwhile, ROS indirectly activates a series of signaling casc...
Source: Current Cancer Drug Targets - September 26, 2016 Category: Cancer & Oncology Authors: Qiao L, Fu N, Yao H, Yuemin N Tags: Curr Cancer Drug Targets Source Type: research

UDP-N-acetyl-D-galactosamine: Polypeptide N-acetylgalactosaminyltransferase-6 (pp-GalNAc-T6): Role in cancer and prospects as a drug target.
Abstract 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. Abnormally glycosylated forms of mucin 1 (substrate of the enzyme), are used clinically...
Source: Current Cancer Drug Targets - September 22, 2016 Category: Cancer & Oncology Authors: Banford S, Timson DJ Tags: Curr Cancer Drug Targets Source Type: research

Stem Cell Transplantation In Multiple Myeloma.
Abstract 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 stron...
Source: Current Cancer Drug Targets - September 19, 2016 Category: Cancer & Oncology Authors: Offidani M, Gentili S, Gay F, Aghemo E, Maracci L, Corvatta L, Palumbo A Tags: Curr Cancer Drug Targets Source Type: research

LRIGs: A Prognostically Significant Family with Emerging Therapeutic Competence against Cancers.
Abstract 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. Moreover, LRIG3 has been shown to act in an opposite manner to LRIG1 and LRIG1,...
Source: Current Cancer Drug Targets - September 7, 2016 Category: Cancer & Oncology Authors: Malik U, Javed A Tags: Curr Cancer Drug Targets Source Type: research

Grid-Independent Descriptors (GRIND) analysis and SAR Guided Molecular Docking Studies to Probe Selectivity Profiles of Inhibitors of Multidrug Resistance Transporters ABCB1 and ABCG2.
Abstract 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 con...
Source: Current Cancer Drug Targets - August 31, 2016 Category: Cancer & Oncology Authors: Shafi T, Jabeen I Tags: Curr Cancer Drug Targets Source Type: research

Functional and clinical significance of the integrin alpha chain CD49d expression in chronic lymphocytic leukemia.
Abstract 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-invo...
Source: Current Cancer Drug Targets - August 9, 2016 Category: Cancer & Oncology Authors: Bo MD, Tissino E, Benedetti D, Caldana C, Bomben R, Del Poeta G, Gaidano G, Rossi FM, Bulian P, Zucchetto A, Gattei V Tags: Curr Cancer Drug Targets Source Type: research

Editorial (Thematic Issue: Targeted Anti-Cancer Drug Delivery).
PMID: 27452678 [PubMed - in process] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - July 28, 2016 Category: Cancer & Oncology Authors: Liang F, Chen B, Zhang C Tags: Curr Cancer Drug Targets Source Type: research

Synthetic Lethal Interactions in Cancer Therapy.
Abstract 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. One promising candidate is a poly...
Source: Current Cancer Drug Targets - July 5, 2016 Category: Cancer & Oncology Authors: Geng X, Wang X, Zhu D, Ying S Tags: Curr Cancer Drug Targets Source Type: research

Targeting Aurora A kinase with Alisertib (ALS) Induces Autophagy and Cell Cycle Arrest and Increases Chemosensitivity in Hepatoblastoma HepG2 Cells.
CONCLUSIONS: ALS exerted anticancer effects in both monotherapy and combinational therapy in HepG2 cells. Autophagy inhibition may promote the anticancer effect of ALS and sensitize the chemotherapy in HepG2 cells. PMID: 27396604 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - June 30, 2016 Category: Cancer & Oncology Authors: Zhu Q, Yu X, Zhou ZW, Zhou C, Chen XW Tags: Curr Cancer Drug Targets Source Type: research

Urotensin-II receptor: a double identity receptor involved in vasoconstriction and in the development of digestive tract cancers and other tumors.
In conclusion, a new weapon in the treatment of human cancers is highlighting a new scenario for the future. PMID: 27338741 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - June 20, 2016 Category: Cancer & Oncology Authors: Federico A, Zappavigna S, Dallio M, Misso G, Merlino F, Loguercio C, Novellino E, Paolo Grieco PX, Caraglia M Tags: Curr Cancer Drug Targets Source Type: research

High-throughput drug screening identifies pyrimethamine as a potent and selective inhibitor of acute myeloid leukemia.
Abstract 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 severa...
Source: Current Cancer Drug Targets - June 16, 2016 Category: Cancer & Oncology Authors: Murphy C, Blanchard J, Ganser A, Brown E, Hassell J, Humpheries RK, Morgan M, Heuser M Tags: Curr Cancer Drug Targets Source Type: research

Molecular Targeted Magnetic Resonance Imaging of Human Colorectal Carcinoma (LoVo) Cells Using Novel Superparamagnetic Iron Oxide- Loaded Nanovesicles: In Vitro and in vivo Studies.
Abstract OBJECTIVE: To investigate the feasibility of superparamagnetic iron oxide (SPIO) nanoparticles (SPIO) as a magnetic resonance (MR) contrast agent to enhance tumor imaging in vivo. METHODS: Hydrophobic SPIO (oil-soluble SPIO; OSPIO) and hydrophilic SPIO (water-soluble SPIO; WSPIO) were loaded in methoxy-poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles. Three groups of nude mice (n=12/group) xenografted with human colorectal carcinoma (LoVo) cells were injected into the caudal vein with WSPIO, OSPIO-loaded nanovesicles, or WSPIO-loaded nanovesicles. MRI scans were performed on...
Source: Current Cancer Drug Targets - June 3, 2016 Category: Cancer & Oncology Authors: Feng ST, Li H, Luo Y, Cai H, Dong Z, Fang Z, Shuai X, Li ZP Tags: Curr Cancer Drug Targets Source Type: research

Targeting key metabolic enzymes involved in lipid and protein biosyntheses for breast anticancer therapies.
Abstract The evolution of genomic research enabled the genetic and molecular profiling of breast cancer and revealed the profound complexity and heterogeneity of this disease. Subtypes of breast cancer characterized by mutations and/or amplifications of some proto-oncogenes are associated with an increased rate of recurrence and poor prognosis. They represent a challenge in the clinic with limited arsenal to attack them. Nowadays, metabolic reprogramming is firmly established as a hallmark of cancer. An increased rate of lipid and protein syntheses in cancerous tissues, a direct consequence of alterations in key m...
Source: Current Cancer Drug Targets - June 3, 2016 Category: Cancer & Oncology Authors: Guerram M, Hamdi AM, Zhang LY, Jiang Z Tags: Curr Cancer Drug Targets Source Type: research

G9a - an Appealing Antineoplastic Target.
Abstract G9a is the primary enzyme for mono- and dimethylation at Lys 9 of histone H3 (H3K9me1 and H3K9me2) and forms predominantly the heteromeric complex as a G9a-GLP (G9a-like protein) that is a functional histone lysine methltransferase in vivo. Mounting evidence suggests that G9a catalyzes methylation of histone and nonhistone proteins, which plays a crucial role in diverse biological processes and human diseases. G9a have attracted great attention of scientists as an appealing antineoplastic target. Here, we review the current knowledge on biological functions of G9a, with particular emphasis on regulating g...
Source: Current Cancer Drug Targets - May 12, 2016 Category: Cancer & Oncology Authors: Chen WL, Sun HP, Li DD, Wang ZH, You QD, Guo XK Tags: Curr Cancer Drug Targets Source Type: research

Recent Advances in Site Specific Conjugations of Antibody Drug Conjugates (ADCs).
Abstract Antibody-drug conjugates (ADCs) take the advantage of antigen specificity of monoclonal antibodies to deliver highly potent cytotoxic drugs selectively to antigen-expressing tumor cells. The recent approval of Adcetris™ and Kadcyla™ as well as emerging data from numerous ongoing clinical trials underscore the role of ADCs as a new therapeutic option for cancer patients. However, conventional conjugation methods generally result in a heterogeneous mixture of ADCs, which can result in significant therapeutic liabilities and can lead to complicated manufacturing processes. The increased understan...
Source: Current Cancer Drug Targets - May 12, 2016 Category: Cancer & Oncology Authors: Gao W, Zhang J, Xiang J, Zhang L, Wu C, Dhal PK, Chen B Tags: Curr Cancer Drug Targets Source Type: research

Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde.
Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde. Curr Cancer Drug Targets. 2016 Apr 26; Authors: Chen TW, Tsai KD, Yang SM, Wong HY, Liu YH, Cherng J, Chou KS, Wang YT, Cuizon J, Cherng JM Abstract Cinnamomum verum is used to make the spice cinnamon and has been used for more than 5000 years by both of the two most ancient forms of medicine in the words: Ayurveda and traditional Chinese herbal medicines for various applications such as a...
Source: Current Cancer Drug Targets - April 26, 2016 Category: Cancer & Oncology Authors: Chen TW, Tsai KD, Yang SM, Wong HY, Liu YH, Cherng J, Chou KS, Wang YT, Cuizon J, Cherng JM Tags: Curr Cancer Drug Targets Source Type: research

CYR61 contributes to poor response to letrozole in ER positive breast carcinoma.
This study provides evidence that CYR61 maycontribute to poor response to letrozole treatment and targeting CYR61 may improve endocrine resistance in ER-positive breast cancer. PMID: 27113745 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - April 26, 2016 Category: Cancer & Oncology Authors: Jia X, Liu G, Cheng J, Shen Z, Shao Z Tags: Curr Cancer Drug Targets Source Type: research

Synthetic lethal interactions in cancer therapy.
Abstract 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. One promising candidate is a poly...
Source: Current Cancer Drug Targets - April 26, 2016 Category: Cancer & Oncology Authors: Geng X, Wang X, Zhu D, Ying S Tags: Curr Cancer Drug Targets Source Type: research

Deregulation of apoptosis - is it still an important issue in pathogenesis of chronic lymphocytic leukemia?
Abstract Chronic lymphocytic leukemia (CLL), a clonal expansion of B CD5+ cells, is the most common type of adult leukemia in western countries. The accumulation of neoplastic B-cells is primarily caused by prolonged life-span of these cells due to deregulation of apoptosis, and only marginally due to a higher proliferation rate. In spite of numerous reports characterizing particular mechanisms of B-CLL cell apoptosis, still relatively little is known about the complex regulation of this process. Therefore, more detailed research is required to understand the complicated mechanisms and regulatory processes of apop...
Source: Current Cancer Drug Targets - April 26, 2016 Category: Cancer & Oncology Authors: Podhorecka M, Macheta A, Bozko M, Bozko A, Malek NP, Bozko P Tags: Curr Cancer Drug Targets Source Type: research

Refractory Chronic Lymphocytic Leukemia: a Therapeutic Challenge.
Abstract Despite impressive therapeutic progress represented by the advent of chemoimmunotherapy, chronic lymphocytic leukemia (CLL) remains incurable by conventional modalities. Refractory CLL defined by non-response to treatment or relapse/progression within 6 months is associated with multiple unfavourable prognostic factors such as p53 pathway disruption, deteriorating patient condition, increased risk of severe infections, and poor response to treatment, resulting in a very short overall survival. Therefore, refractory CLL represents a highly challenging situation for the hematologist as well as the patient. ...
Source: Current Cancer Drug Targets - April 8, 2016 Category: Cancer & Oncology Authors: Smolej L Tags: Curr Cancer Drug Targets Source Type: research

Therapeutic Approach to Patients with Chronic Lymphocytic Leukemia and Significant Comorbid Conditions.
Abstract Clinical trials in chronic lymphocytic leukemia (CLL) have focused mainly on younger fit patients until recently. However, CLL is a disease of elderly and many patients have significant comorbid conditions which together with advanced age preclude the use of aggressive regimens like FCR (fludarabine, cyclophosphamide, rituximab). Therefore, parameters such as performance status, renal function and number/severity of comorbidities together with clinical judgment should be used to guide the decision-making process regarding intensity of treatment. Two large randomized trials recently demonstrated that addit...
Source: Current Cancer Drug Targets - April 8, 2016 Category: Cancer & Oncology Authors: Smolej L Tags: Curr Cancer Drug Targets Source Type: research

Mechanistic and clinical aspects of lenalidomide treatment for chronic lymphocytic leukemia.
Abstract There have been significant advances in our understanding of the pathogenesis of chronic lymphocytic leukemia (CLL) over the last decade, which has been accompanied by a rapid increase in treatment options. Inhibitors of BCR-signaling such as ibrutinib and idelalisib, and pro-apoptotic agents such as ABT-199 have shown great promise in initial clinical trials and have been at the forefront of recent developments. However, despite the encouraging early data, these agents do not appear to represent a "cure" for CLL and mechanisms of resistance to these agents have already been identified. In light...
Source: Current Cancer Drug Targets - April 8, 2016 Category: Cancer & Oncology Authors: Riches JC, Gribben JG Tags: Curr Cancer Drug Targets Source Type: research

Targeting signaling pathways in chronic lymphocytic leukemia.
Abstract Various signal transduction pathways have been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), which is characterized by the progressive accumulation of monoclonal CD5+ B cells in the blood. B cell receptor (BCR) signaling appears to have a crucial role in disease onset and is thought to be induced by self- or non-self-antigen recognition leading to chronic stimulation. Several of the kinases functioning downstream of the BCR are aberrantly expressed or constitutively activated in CLL. Yet, these kinases have additional roles, particularly in chemokine receptor signaling, which is es...
Source: Current Cancer Drug Targets - April 8, 2016 Category: Cancer & Oncology Authors: Muggen AF, Singh SP, Hendriks RW, Langerak AW Tags: Curr Cancer Drug Targets Source Type: research

Mechanisms and Therapeutic Targets of microRNA-associated Chemoresistance in Epithelial Ovarian Cancer.
Abstract Epithelial ovarian cancer (EOC) is the most lethal disease among gynecologic malignancies. Despite increasing knowledge of ovarian cancer biology and advances in treatment efficacy, the survival rate of patients with EOC has not improved over the past two decades. Patients with an advanced disease often relapse due to the development of chemoresistance. Recent in vivo and in vitro studies have shown insight into the mechanisms of such drug resistance, including a potential role for microRNAs (miRNA, miR) in the process of chemoresistance. In this review, we provide an overview of current therapeutic targe...
Source: Current Cancer Drug Targets - April 4, 2016 Category: Cancer & Oncology Authors: Zhang L, Nadeem L, Connor K, Xu G Tags: Curr Cancer Drug Targets Source Type: research

Pax5 Re-Expression In H460 Cells Treated With The Combination Of Demethylating Agent And Histone Deacetylase Inhibitor Is Associated With The Enhancement Of P53 Binding To Pax5 Promoter Region.
In this study, we used epigenetic combination of Aza and HDAC inhibitor Vorinostat (SAHA) to treat NSCLC cells and tried to elucidate the underlying molecular mechanism. We treated pax5-silenced NSCLC H460 cells with Aza+SAHA combination at sub-toxic concentration and detected the re-expression of pax5 mNRA and protein. Our MassArray illustrated demethylation of CpG sites in pax5 promoter region by Aza treatment; and DNA-protein binding assay indicated increased DNA accessibility for protein binding by SAHA treatment. Chromatin DNA-protein binding test demonstrated that the combination of Aza+SAHA significantly increased p...
Source: Current Cancer Drug Targets - March 31, 2016 Category: Cancer & Oncology Authors: Liang Y, Zeng J, Jelicks L, Ma S, Liu J, Mei J, Perez-Soler R, Zou Y Tags: Curr Cancer Drug Targets Source Type: research

Understanding molecular pathways and targets of Brachyury in epithelial-mesenchymal transition (EMT) in human cancers.
Abstract Brachyury is an important transcription factor of the T-box gene family with an evolutionarily-conserved function in mesoderm development in the embryo. Recent research has demonstrated that, in various human carcinomas, overexpression of Brachyury is associated with epithelial-mesenchymal transition (EMT), tumor metastasis, expression of markers for cancer stem cells, and resistance to chemotherapy and radiotherapy. Brachyury is a diagnostic and prognostic biomarker, and its expression in tumor tissues is associated with increasing tumor grade, stage, invasiveness, metastasis and poor prognosis. Targetin...
Source: Current Cancer Drug Targets - March 28, 2016 Category: Cancer & Oncology Authors: Songa W, Gobe GC Tags: Curr Cancer Drug Targets Source Type: research

Current Strategy for Cisplatin Delivery.
Abstract Cisplatin is one of the leading chemotherapy drugs currently used in clinical settings. However, its serious side effects and its resistance developed by tumor cells hinder its usage. To decrease its side effects and maintain anti-cancer efficiency, various cisplatin based formulations were developed. In this minireview, we summarized the recent progress of cisplatin delivery strategies, including direct delivery, prodrug delivery and combination delivery. Key challenges preventing the development of improved drug formulations were identified, and effective approaches to address these issues were discusse...
Source: Current Cancer Drug Targets - March 28, 2016 Category: Cancer & Oncology Authors: Yue Z, Cao Z Tags: Curr Cancer Drug Targets Source Type: research

Small Molecules Targeting Ataxia Telangiectasia and Rad3-Related (ATR) Kinase: An Emerging way to Enhance Existing Cancer Therapy.
Abstract The main aim of current cancer research is to find a way to selectively affect the tumor cells, while leaving normal cells intact. Ataxia telangiectasia and Rad3-related kinase (ATR), a member of the phosphatidylinositol-3-related protein kinases (PIKK), represents a candidate target for achieving this goal. ATR kinase is one of the main kinases of the DNA damage response signaling pathway and responds to DNA damage caused by replication stress and various genotoxic agents (i.e. chemotherapy, ionizing radiation, ultraviolet light). ATR activation triggers cell cycle checkpoints, DNA repair and apoptosis, ...
Source: Current Cancer Drug Targets - February 19, 2016 Category: Cancer & Oncology Authors: Andrs M, Korabecny J, Nepovimova E, Jun D, Hodny Z, Kuca K Tags: Curr Cancer Drug Targets Source Type: research

Role of Liprins in the Regulation of Tumor Cell Motility and Invasion.
Abstract Invasion leading to the formation of metastasis is one of the hallmarks of cancer. Analysis of different human cancers has led to the identification of the PPFIA1 gene encoding the protein liprin-α1, a possible player in cancer. The PPFIA1 gene is amplified in malignant tumors, including about 20% of breast cancers. Also the liprin-α1 protein is found overexpressed in tumors. Liprin-α1 belongs to the liprin family of cytosolic scaffold proteins that includes four liprin-α, two liprin-β members, and liprin-γ/kazrinE. In this review we will discuss the available evidence o...
Source: Current Cancer Drug Targets - February 19, 2016 Category: Cancer & Oncology Authors: Chiaretti S, Curtis Id Tags: Curr Cancer Drug Targets Source Type: research

The Novel VEGF121-VEGF165 Fusion Attenuates Angiogenesis and Drug Resistance via Targeting VEGFR2-HIF-1α-VEGF165/Lon Signaling Through PI3K-AKT-mTOR Pathway.
In conclusion, our data demonstrated that the chimeric VEGF121-VEGF165 arrests the tube formation of endothelial cells and interferes with tumor cell growth, migration and invasion, suggesting that it could be a potential drug as an angiogenesis antagonist in cancer therapy. The VEGF121-VEGF165 targets not only paracrine angiogenic cascade of endothelial cells but also autocrine PI3K-AKT-mTOR-mediated VEGFR2-HIF-1α- VEGF165/Lon signaling that drives drug resistance in tumor cells. Our study will open up the patient opportunities to combat drug resistance to antiangiogenic therapy. PMID: 26882030 [PubMed - in pro...
Source: Current Cancer Drug Targets - February 19, 2016 Category: Cancer & Oncology Authors: Tsai JL, Lee YM, Pan CY, Lee AY Tags: Curr Cancer Drug Targets Source Type: research

E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets.
E2F1 and NF-κB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets. Curr Cancer Drug Targets. 2016 Feb 16; Authors: Huang Y, Chen R, Zhou J Abstract Inflammation is the fundamental protective immuno-response and frequently occurred in organisms including humen beings. However, disordered response can cause chronic human disease, including cancer. Inflammatory cells and mediators are essential to the tumor microenvironment, and dissection of this complex molecular and cellular milieu may elucidate a connection between cancer and inflammation. Thus, focusing on tran...
Source: Current Cancer Drug Targets - February 16, 2016 Category: Cancer & Oncology Authors: Huang Y, Chen R, Zhou J Tags: Curr Cancer Drug Targets Source Type: research

OncomicroRNAs-mediated tumorigenesis: implication in cancer diagnosis and targeted therapy.
Abstract MicroRNAs (miRNAs) control the expression of approximately 60% of protein-coding genes and regulate cell metabolism, proliferation, differentiation, and apoptosis. Notably, aberrant expression of miRNAs contributes to several diseases including cancer. Accumulating evidence indicates that miRNAs play important roles in EMT, genesis of cancer stem cells, cancer metabolism and carcinogenesis. Aberrant expression of miRNAs triggers tumor initiation,progression and poor prognosis of cancer patients. Accordingly, oncogenic miRNAs have emerged as diagnostic biomarkers and targets for novel anti-cancer drug di...
Source: Current Cancer Drug Targets - February 16, 2016 Category: Cancer & Oncology Authors: Zheng N, Yang P, Wang Z, Zhou Q Tags: Curr Cancer Drug Targets Source Type: research

Current Development of ROS-Modulating Agents as Novel Antitumor Therapy.
Abstract Compared to normal cells, usually cancer cells are under higher oxidative stress. Elevating intracellular levels of reactive oxygen species (ROS) by introducing excessive ROS or inhibiting antioxidant system may enhance selectively of cancer cell killing by ROS-modulating agents through stress sensitization or stress overload. Meanwhile due to the adaptive response, normal cells may be capable of maintaining redox homeostasis under exogenous ROS. Here we review ROS-modulating agents in different mechanisms and classify them into groups by various targets for illustrating more clearly. At last, we discuss ...
Source: Current Cancer Drug Targets - February 16, 2016 Category: Cancer & Oncology Authors: Wang N, Wu Y, Bian J, Qian X, Lin H, Sun H, You Q, Zhang X Tags: Curr Cancer Drug Targets Source Type: research

MT1-MMP Activation of TGF-β Signaling Enables Intercellular Activation of an Epithelial-mesenchymal Transition Program in Cancer.
MT1-MMP Activation of TGF-β Signaling Enables Intercellular Activation of an Epithelial-mesenchymal Transition Program in Cancer. Curr Cancer Drug Targets. 2016 Feb 16; Authors: Nguyen HL, Kadam P, Cao K, Wu S, Samara GJ, Zhang Q, Zucker S, Cao J Abstract Membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) is associated with cancer invasion and metastasis leading to poor patient prognosis. MT1-MMP mediates cancer cell invasion via degradation of basement membrane and extracellular matrix, and induction of cell migration. However, MT1-MMP expression in the cancer stroma can drive invasion o...
Source: Current Cancer Drug Targets - February 16, 2016 Category: Cancer & Oncology Authors: Nguyen HL, Kadam P, Cao K, Wu S, Samara GJ, Zhang Q, Zucker S, Cao J Tags: Curr Cancer Drug Targets Source Type: research

Bispecific Antibodies for Targeted Delivery of Dendritic Polyglycerol (dPG) Prodrug Conjugates.
This study demonstrates the potential of digoxigeninylated dPG prodrug conjugates in combination with bsAbs as a new platform for targeted prodrug delivery into cancerous tissues. However the nanoparticle design needs to be further optimized for significant targeted delivery. PMID: 26853135 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - February 8, 2016 Category: Cancer & Oncology Authors: Mehrabadi FS, Adelmann J, Gupta S, Wedepohl S, Calderón M, Brinkmann U, Haag R Tags: Curr Cancer Drug Targets Source Type: research

miR-137 suppresses the phosphorylation of AKT and improves the dexamethasone sensitivity in multiple myeloma cells via targeting MITF.
In this study, the target gene and the potential effect of miR-137 in MM were investigated. The results showed significantly downregulated expression of miR-137 in MM cell lines and in the CD138+ bone marrow mononuclear cells of MM patients. A dual luciferase reporter gene analysis revealed that MITF is a direct target of miR-137. The overexpression of miR-137 or transfection of MITF-shRNA had no significant effect on the expression of serine/threonine protein kinase (AKT), but the expression of MITF, c-MET, p-AKT, and its phosphorylated substrate protein decreased significantly, which was accompanied by an increase in p53...
Source: Current Cancer Drug Targets - February 2, 2016 Category: Cancer & Oncology Authors: Zhang B, Ma L, Wei J, Hu J, Zhao Z, Wang Y, Chen Y, Zhao F Tags: Curr Cancer Drug Targets Source Type: research

BRCA1-associated triple-negative breast cancer and potential treatment for ruthenium-based compounds.
Abstract Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). The clinicopathological characteristics of TNBC include a high grading, a high rate of cell proliferation and a greater degree of chromosomal rearrangement. Patients with triple-negative breast cancer are more likely to be drug resistant and more difficult to treat, and are also frequently BRCA1 mutants. Methylation of the BRCA1 promoter region is associated with a reduction of t...
Source: Current Cancer Drug Targets - February 2, 2016 Category: Cancer & Oncology Authors: Hongthong K, Ratanaphan A Tags: Curr Cancer Drug Targets Source Type: research