Proteomic and Metabolic Signatures of Esophageal Squamous Cell Carcinoma.
We report the association of ACPP, C2orf54, DYNLT3, ENDOU, FMO2, and KANK1 (down-regulated genes) and COL10A1, FNDC3B, HOMER3, MARCKSL1, and RFC4 (up-regulated genes) to ESCC for the first time. Further, the ESCC driven molecular pathways were also constructed to elucidate the molecular mechanism of the disease; specifically several metabolic pathways were down-regulated while the signaling pathways were up-regulated. Additionally, reporter metabolites for ESCC were analyzed and metabolic dysfunction was ascertained in arachidonic acid metabolism and steroid hormone biosynthesis pathways. The multi-omics network strategy p...
Source: Current Cancer Drug Targets - February 2, 2016 Category: Cancer & Oncology Authors: Karagoz K, Lehman HL, Stairs DB, Sinha R, Arga KY Tags: Curr Cancer Drug Targets Source Type: research

Editorial: Ubiquitin E3 Ligases as Molecular Targets or Tools for Advanced Cancer Therapy.
PMID: 26791134 [PubMed - in process] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - January 24, 2016 Category: Cancer & Oncology Authors: Kitagawa M Tags: Curr Cancer Drug Targets Source Type: research

Anticancer Potential and Molecular Targets of Pristimerin: A mini-review.
Abstract Pristimerin, a natural triterpenoid isolated form Celastrus and Maytenus spp, has been shown to possess a variety of biological and pharmacological effects. Recently, pristimerin has attracted more attention, especially for its potential anticancer activities. The anticancer activities of pristimerin have been illustrated in various cancer cell lines and animal models. It has been found to inhibit in vitro and in vivo proliferation, survival, angiogenesis and metastasis of tumor cells. These activities have been attributed to its modulation of various molecular targets such as cyclins, apoptosis-related p...
Source: Current Cancer Drug Targets - January 11, 2016 Category: Cancer & Oncology Authors: Yousef BA, Hassan HM, Zhang LY, Jiang ZZ Tags: Curr Cancer Drug Targets Source Type: research

RBM15 functions in Blood diseases.
Abstract RBM15, an RNA-binding protein, plays important roles in the growth and apoptosis of cells, especially blood cells through regulating multiple signal pathways such as Notch and Wnt. An increasing body of evidence has suggested that RBM15 may play a key function on the development of various blood diseases, such as acute/chronic myeloid leukemia,kaposi's sarcoma. In this review, we will focus on the progress of the association between RBM15 and its related blood diseases. PMID: 26758534 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - January 11, 2016 Category: Cancer & Oncology Authors: Hu M, Yang Y, Ji Z, Luo J Tags: Curr Cancer Drug Targets Source Type: research

Roles of interferon regulatory factors in chronic myeloid leukemia.
ROLES OF INTERFERON REGULATORY FACTORS IN CHRONIC MYELOID LEUKEMIA. Curr Cancer Drug Targets. 2016 Jan 4; Authors: Manzella L, Tirrò E, Pennisi MS, Massimino M, Stella S, Romano C, Vitale SR, Vigneri P Abstract The Interferon Regulatory Factor (IRF) family consists of multiple transcription factors involved in the regulation of a variety of biological processes. Originally identified as transcriptional regulators of the type I interferon system, IRFs play a pivotal role in adaptive immunity, cell growth, differentiation and tumorigenesis. Hence, understanding IRF biology has important implicati...
Source: Current Cancer Drug Targets - January 4, 2016 Category: Cancer & Oncology Authors: Manzella L, Tirrò E, Pennisi MS, Massimino M, Stella S, Romano C, Vitale SR, Vigneri P Tags: Curr Cancer Drug Targets Source Type: research

nMET, a new target in recurrent cancer.
Abstract Membranous Met is classically identified with its role in cancer metastases, while nuclear Met is associated with a more invasive, aggressive and proliferative form of cancer. Full-length Met or N-terminal transmembrane domain cleaved Met can translocate into nucleus in a cell growth and pH dependent but ligand-dependent (full length Met) and -independent (cleaved Met) manner. nMET may play greater essential roles in cancer recurrence than membranous Met. For example in prostate cancer, it has been found that androgen receptor (AR) may inhibit the expression of membranous Met so anti-androgen based prosta...
Source: Current Cancer Drug Targets - January 4, 2016 Category: Cancer & Oncology Authors: Xie Y, Istayeva S, Chen Z, Tokay T, Zhumadilov Z, Wu D, Hortelano G, Zhang J Tags: Curr Cancer Drug Targets Source Type: research

Preferentially Expressed Antigen in Melanoma (PRAME) and the PRAME family of Leucine-Rich Repeat Proteins".
Preferentially Expressed Antigen in Melanoma (PRAME) and the PRAME family of Leucine-Rich Repeat Proteins". Curr Cancer Drug Targets. 2015 Dec 22; Authors: Hermesa N, Kewitza S, Staege MS Abstract Preferentially expressed antigen in melanoma (PRAME) is the best characterized member of the PRAME family of leucine-rich repeat (LRR) proteins. Mammalian genomes contain multiple members of the PRAME family whereas in other vertebrate genomes only one PRAME-like LRR protein was identified. PRAME is a cancer/testis antigen that is expressed at very low levels in normal adult tissues except testis but at...
Source: Current Cancer Drug Targets - December 22, 2015 Category: Cancer & Oncology Authors: Hermesa N, Kewitza S, Staege MS Tags: Curr Cancer Drug Targets Source Type: research

Lactate transporters and pH regulation: potential therapeutic targets in glioblastomas.
zar F Abstract Despite advances in therapy, glioblastoma (GBM) is still the most prevalent and lethal brain tumor. Thus, it is imperative to identify new and effective therapies that could improve the lifetime of these patients. It is known that tumor cells, such as glioblastomas present a metabolic reprogramming, named "Warburg effect", recognized nowadays as a hallmark of cancer. This mechanism is associated with a high dependence of tumor cells on the glycolytic metabolism to sustain energy demands and macromolecule synthesis, leading to production of high amounts of lactic and carbonic acid. These me...
Source: Current Cancer Drug Targets - December 22, 2015 Category: Cancer & Oncology Authors: Miranda-Gonçalves V, Reis RM, Baltazar F Tags: Curr Cancer Drug Targets Source Type: research

Epigenetic Targeting of Platinum Resistant Testicular Cancer.
Abstract The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, little is known of the epigenetic alterations in testicular cancer and particularly in platinum refractory germ cell tumors. Germ cell derived testicular cancers, as compared to somatic tumors, appear to have a unique epigenetic profile that features more extensive DNA hypomethylation. Emerging data from clinical specimens suggests that epigenetic aberrations, especially DNA hypermethylation, can contribute to chemotherapy resistance and poor clinical outcomes in testicular germ cell tu...
Source: Current Cancer Drug Targets - December 22, 2015 Category: Cancer & Oncology Authors: Sonnenburg D, Spinella MJ, Albany C Tags: Curr Cancer Drug Targets Source Type: research

Comparative proteomic profiling of extracellular proteins between normal and gastric cancer cells.
In this study, iTRAQ-based liquid chromatography/tandem mass spectrometry was used for comparative profiling of the secretomes of 11 gastric cancer cell lines versus a normal gastric epithelial cell line. Of the close to 800 proteins detected, about 600 proteins were detected to display differential expression in one or more gastric cancer cell lines compared to normal cells. These differentially expressed proteins predominantly have binding or enzymatic activities and are largely associated with cellular and metabolic processes. Overexpression of ARPC4 was validated in gastric cell lines and its novel function in gastric ...
Source: Current Cancer Drug Targets - December 8, 2015 Category: Cancer & Oncology Authors: Mulina, Lu S, Chong PK, Yeoh KG, Lim YP Tags: Curr Cancer Drug Targets Source Type: research

Epi-drugs and Epi-miRs: Moving beyond current cancer therapies.
Abstract Epigenetic modifications determine phenotypic characteristics in a reversible, stable and genotype-independent manner; Epigenetic modifications mainly encompass CpG island methylation and histone modifications, both being important in the pathogenesis of malignancies. The reversibility of epigenetic phenomenon provides a suitable therapeutic option that is reactivation of epigenetically silenced tumor-suppressor genes. Inhibition of DNA methyltransferase, histone deacetylase and Aurora B kinase, individually or collectively, could feasibly prevent or inverse the impact of epigenetic silencing. MicroRNAs (...
Source: Current Cancer Drug Targets - December 6, 2015 Category: Cancer & Oncology Authors: Salarini R, Sahebkar A, Mirzaei HR, Jaafari MR, Riahi MM, Hadjati J, Asrami MO, Fdaee S, Salehi R, Mirzaei H Tags: Curr Cancer Drug Targets Source Type: research

Advances in Synergistic Combinations of Chinese Herbal Medicine for the Treatment of Cancer.
Abstract The complex pathology of cancer development requires correspondingly complex treatments. The traditional application of individual single-target drugs fails to sufficiently treat cancer with durable therapeutic effects and tolerable adverse events. Therefore, synergistic combinations of drugs represent a promising way to enhance efficacy, overcome toxicity and optimize safety. Chinese Herbal Medicines (CHMs) have long been used as such synergistic combinations. Therefore, we summarized the synergistic combinations of CHMs used in the treatment of cancer and their roles in chemotherapy in terms of enhancin...
Source: Current Cancer Drug Targets - December 6, 2015 Category: Cancer & Oncology Authors: Hu XQ, Sun Y, Lau E, Zhao M, Su SB Tags: Curr Cancer Drug Targets Source Type: research

S-equol, a Secondary Metabolite of Natural Anticancer Isoflavone Daidzein, Inhibits Prostate Cancer Growth In Vitro and In Vivo, Though Activating the Akt/FOXO3a Pathway.
Abstract Forkhead box O3 (FOXO3a) is a transcription factor with tumor suppressor functions that plays an important role in prostate cancer. Daidzein, one of the soy isoflavones present in soy-based foods, has been shown to exert anti-tumor effects in vitro and in vivo. We herein investigated the inhibitory effects of S-equol, an isoflavandiol metabolized from daidzein by bacterial flora in the intestines, on the LnCaP, DU145 and PC3 human prostate cancer cell lines. Our results showed that S-equol and R-equol inhibited the growth of all three cell lines. Additional studies revealed that S-equol caused cell cycle ...
Source: Current Cancer Drug Targets - December 6, 2015 Category: Cancer & Oncology Authors: Lu Z, Zhou R, Kong Y, Wang J, Xia W, Guo J, Liu J, Sun H, Liu K, Yang J, Mi M, Xu H Tags: Curr Cancer Drug Targets Source Type: research

Peptides to Target Tumor Vasculature and Lymphatics for Improved Anti-Angiogenesis Therapy.
Abstract Cancer has become one of the leading causes of increased mortality. The currently employed diagnostic and therapeutic modality offer only minimal specificity towards cancerous cells and affects normal healthy cells. Targeted drug delivery systems have shown an improved efficiency in the diagnosis and treatment of various cancers, as these targeted molecules specifically reaches the tumor cells alone without exerting any undesirable effects on the normal healthy cells. Recent finding have shown that disruption of blood vasculature and lymphatics is efficient in treating various cancers. As these vessels su...
Source: Current Cancer Drug Targets - November 30, 2015 Category: Cancer & Oncology Authors: Sivashankari PR, Prabaharan M Tags: Curr Cancer Drug Targets Source Type: research

Nanoparticles for Colorectal Cancer-Targeted Drug Delivery and MR Imaging: Current Situation and Perspectives.
Abstract The application of nanoparticles (NPs) offers new prospects for the early detection and effective treatment of colorectal cancer (CRC). Various NPs have been designed and explored as diagnostic and/or therapeutic drug delivery vehicles. To achieve selective treatment and to reduce toxicity, these nanoparticles are usually endowed with targeting abilities. Passive targeting is based on the extravasation and enhanced permeability and retention effect of tumors, while active targeting always involves binding to specific ligands that are recognizable by CRC tissues, such as vascular endothelial growth factor,...
Source: Current Cancer Drug Targets - November 30, 2015 Category: Cancer & Oncology Authors: Dong Z, Cui MY, Peng Z, Li Y, Wang X, Fang Z, Jiang M, Xu L, Luo Y, Li ZP, Feng ST Tags: Curr Cancer Drug Targets Source Type: research

Targeting Tumors with Small Molecule Peptides.
Abstract Chemotherapeutic treatment of cancers is a challenging endeavor, hindered by poor selectivity towards tumorous tissues over healthy ones. Preferentially delivering a given drug to tumor sites necessitates the use of targeting elements, of which there are a wide range in development. In this Review, we highlight recent examples of peptide-based targeting ligands that have been exploited to selectively deliver a chemotherapeutic payload to specific tumor-associated sites such as the vasculature, lymphatics, or cell surface. The advantages and limitations of such approaches will be discussed with a view to p...
Source: Current Cancer Drug Targets - November 30, 2015 Category: Cancer & Oncology Authors: Cheetham AG, Keith D, Zhang P, Lin R, Su H, Cui H Tags: Curr Cancer Drug Targets Source Type: research

Targeted Delivery of Bleomycin: a Comprehensive Anticancer Review.
Abstract Despite being one of the most effective broad-spectrum chemotherapeutic agents in the treatment of cancers, the clinical applications of bleomycins (BLMs) have been limited due to their poor drug delivery abilities, and the side effect of causing lung fibrosis. Due to the increased therapeutic effects and the reduction of side effects, research and development of targeted drug delivery systems (TDDS) with BLMs has become essential for the expansive clinical usage of BLM based therapeutics. This review summarizes the recent developments of various TDDS for BLMs, including techniques such as photochemical i...
Source: Current Cancer Drug Targets - November 30, 2015 Category: Cancer & Oncology Authors: Yu Z, Yan B, Gao L, Dong C, Zhong J, D Ortenzio M, Nguyen B, Hu X, Liang F Tags: Curr Cancer Drug Targets Source Type: research

Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies.
This article discusses and focuses on using MDM4 as a novel biomarker as well as a therapeutic target for hematologic malignancies. PMID: 26567881 [PubMed - in process] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - November 18, 2015 Category: Cancer & Oncology Authors: Cao L, Fan L, Xu W, Li JY Tags: Curr Cancer Drug Targets Source Type: research

Role of EGFR Monoclonal Antibodies in the Management of Non-small Cell Lung Cancer.
Abstract Dysregulation of epidermal growth factor receptor (EGFR) signaling due to receptor overexpression or activating mutation is associated with cancer cell proliferation, metastasis, and survival. EGFR has become an important therapeutic target for non-small cell lung cancer (NSCLC), and several EGFR-targeted agents, such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs), have been developed. The EGFR-TKIs gefitinib, erlotinib, and afatinib have been approved for the treatment of advanced NSCLC, and sensitivity to these drugs has been shown to be associated with the presence of EGFR mutati...
Source: Current Cancer Drug Targets - November 18, 2015 Category: Cancer & Oncology Authors: Takeda M, Nakagawa K Tags: Curr Cancer Drug Targets Source Type: research

Structural Characterization of Alpha-methylacyl-CoA Racemase: Comparative Structural Modeling, Molecular Docking and Dynamic Simulations Studies.
Abstract α-Methylacyl-CoA racemase (AMACR) has recently been reported as a vital solid tumor marker and is an attractive target for designing anti-tumor agents. It is a mitochondrial and peroxisomal enzyme which plays a central role in the oxidation of cholesterol metabolites and branched chain fatty acids. The three dimensional structure of human AMACR is still unknown. In the current study, homology model using Modeller and different modelling servers based on 1X74A as template is reported. The three dimensional model generated was validated and evaluated using various available programs like PROCHECK, ERR...
Source: Current Cancer Drug Targets - November 18, 2015 Category: Cancer & Oncology Authors: Abbasi SW, Azam SS Tags: Curr Cancer Drug Targets Source Type: research

Targeted inhibition of Rictor/mTORC2 in cancer treatment: a new era after rapamycin.
Abstract The evolutionarily conserved mechanistic target of rapamycin (mTOR) forms two functionally distinct complexes, mTORC1 and mTORC2. mTORC1, consisting of mTOR, raptor, and mLST8 (GβL), is sensitive to rapamycin and thought to control autonomous cell growth in response to nutrient availability and growth factors. mTORC2, containing the core components mTOR, mLST8, Rictor, mSIN1, and Protor1/2 is largely insensitive to rapamycin. mTORC2 specifically senses growth factors and regulates cell proliferation, metabolism, actin rearrangement, and survival. Dysregulation of mTOR signaling often occurs in a vari...
Source: Current Cancer Drug Targets - November 13, 2015 Category: Cancer & Oncology Authors: Zou Z, Chen J, Yang J, Bai X Tags: Curr Cancer Drug Targets Source Type: research

Understanding cancer drug resistance by developing and studying resistant cell line models.
Abstract Despite the enormous number of anticancer drugs presently available in the clinic, treatment failure due to drug resistance is very frequent. The identification of mechanisms of resistance to different drugs is necessary, in order to identify ways to prevent and circumvent such resistance. Indeed, the identification of novel therapeutic targets to overcome cancer drug resistance remains one of the major challenges in drug discovery and development. The methods employed to identify drug resistance mechanisms and novel therapeutic targets depend greatly on the establishment of cancer drug resistant cell lin...
Source: Current Cancer Drug Targets - November 13, 2015 Category: Cancer & Oncology Authors: Xavier CP, Pesic M, Vasconcelos MH Tags: Curr Cancer Drug Targets Source Type: research

Cytochrome P450 2W1 (CYP2W1) in Colorectal Cancers.
Abstract Cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1) is a newly identified monooxygenase enzyme that is expressed specifically in tumor tissues and during fetal life. Particularly, high expression of CYP2W1 was observed in up to 60% of colorectal cancers and its expression correlated with poor survival. CYP2W1 has been shown to metabolize various endogenous substrates including lysophospholipids and several procarcinogens, such as polycyclic aromatic hydrocarbon. The specific substrate for CYP2W1, however, is currently unknown. Due to its tumor-specific expression and its unique catalytic activi...
Source: Current Cancer Drug Targets - November 13, 2015 Category: Cancer & Oncology Authors: Chung FF, Mai CW, Ng PY, Leong CO Tags: Curr Cancer Drug Targets Source Type: research

Potential Therapeutic Approaches For The Treatment Of Acute Myeloid Leukemia With AML1-ETO Translocation.
CONCLUSION: In order to improve the therapeutic regime for AML patients with t(8;21), efforts are required to translate the success achieved in identification of potent candidates for targeted therapy into clinical setup in the best possible combination. PMID: 26563884 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - November 13, 2015 Category: Cancer & Oncology Authors: Arora R, Sawney S, Saluja D Tags: Curr Cancer Drug Targets Source Type: research

RING-, HECT-, and RBR-type E3 Ubiquitin Ligases: Involvement in Human Cancer.
Abstract In the ubiquitylation system, E3 ubiquitin ligases play a key role in determining substrate specificity and catalyzing the transfer of ubiquitin from E2 enzymes to the substrate. Growing evidence has shown that E3 ubiquitin ligases are involved in cancer development and progression. The RING-type and HECT-type E3 ligases are the classically categorized groups of E3 ubiquitin ligases, and more of these enzymes are being shown to be potential targets for cancer therapy. The recently classified RBR E3 ligases catalyze the transfer of ubiquitin by a RING/HECT hybrid-like mechanism. Notably, these ligases are ...
Source: Current Cancer Drug Targets - November 12, 2015 Category: Cancer & Oncology Authors: Uchida C, Kitagawa M Tags: Curr Cancer Drug Targets Source Type: research

Tribbles-Related Protein Family Members as Regulators or Substrates of the Ubiquitin-Proteasome System in Cancer Development.
Abstract Tribbles-related protein (TRB) family members are the mammalian orthologs of Drosophila tribbles. Tribbles was originally identified as a cell cycle regulator during Drosophila development. Tribbles genes are evolutionary conserved, and three TRB genes (TRB1, TRB2 and TRB3) have been identified in mammals. TRBs are considered pseudokinases because they lack an ATP binding site or one of the conserved catalytic motifs essential for kinase activity. Instead, TRBs play important roles in various cellular processes as scaffolds or adaptors to promote the degradation of target proteins and to regulate several ...
Source: Current Cancer Drug Targets - November 12, 2015 Category: Cancer & Oncology Authors: Sakai S, Miyajima C, Uchida C, Itoh Y, Hayashi H, Inoue Y Tags: Curr Cancer Drug Targets Source Type: research

Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy.
Abstract Selective degradation of pathogenic proteins by small molecules in cells is a novel approach for development of therapeutic agents against various diseases, including cancer. We and others have developed a protein knockdown technology with a series of hybrid small compounds, called SNIPERs (Specific and Nongenetic IAP-dependent Protein ERasers); and peptidic chimeric molecules, called PROTACs (proteolysis-targeting chimeric molecules), which induce selective degradation of target proteins via the ubiquitin-proteasome pathway. These compounds include two different ligands connected by a linker; one is a li...
Source: Current Cancer Drug Targets - November 12, 2015 Category: Cancer & Oncology Authors: Ohoka N, Shibata N, Hattori T, Naito M Tags: Curr Cancer Drug Targets Source Type: research

E3 ubiquitin ligases as molecular targets in human oral cancers.
Abstract The ubiquitin-proteasome pathway is involved in various biological processes. Several oncogenic E3 ligases target tumor suppressor proteins for ubiquitin-mediated degradation. Alternatively, some other E3 ligases play as a tumor suppressor specifically targeting oncogene products. Deregulation of these E3 ligases induces unbalance between oncogenic signal and tumor suppressor pathway and leads to cellular transformation, tumor growth and metastasis in various human malignancies including oral, and head and neck cancers. Facilitated degradation of the cyclin-dependent kinase (CDK) inhibitor p27Kip1 has bee...
Source: Current Cancer Drug Targets - November 12, 2015 Category: Cancer & Oncology Authors: Masumoto K, Kitagawa M Tags: Curr Cancer Drug Targets Source Type: research

The SCF-type E3 Ubiquitin Ligases as Cancer Targets.
Abstract The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin-proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-associated protein 2 (SKP2) (also known as FBXL1) is often overexpressed in human cancers, and functions as an oncogenic E3 ligase to degrade tumor suppressor gene products. Moreover, F-box/WD repeat-containing protein 7 (FBXW7) (also known as Fbw7) is often mutated in human cancers and functi...
Source: Current Cancer Drug Targets - November 12, 2015 Category: Cancer & Oncology Authors: Kitagawa K, Kitagawa M Tags: Curr Cancer Drug Targets Source Type: research

Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer.
Abstract Epithelial-mesenchymal transition (EMT) plays an important role in the development of tumor metastases by facilitating cell migration and invasion. One of the hallmarks of EMT is the diminished expression of E-cadherin and gain of mesenchymal traits, which are regulated by core EMT-inducing transcriptional factors (EMT-TFs), such as Snail/Slug, ZEB1/ZEB2, and Twist1. EMT-TFs are known to be extremely labile proteins, and their protein levels are tightly controlled by the ubiquitin-proteasome system (UPS). Several E3 ubiquitin ligases have been shown to play crucial roles in the regulation of EMT, and gene...
Source: Current Cancer Drug Targets - November 12, 2015 Category: Cancer & Oncology Authors: Inoue Y, Itoh Y, Sato K, Kawasaki F, Sumita C, Tanaka T, Morishita D, Hayashi H Tags: Curr Cancer Drug Targets Source Type: research

Is there a place for bevacizumab in patients with extensive-stage small cell lung cancer?
Abstract It was estimated that small cell lung cancer (SCLC) concerns about 15% of all lung cancer cases. Patients with SCLC are usually diagnosed in advanced stage of disease. Unfortunately at this stage, prognosis is very poor. Bevacizumab is a monoclonal antibody against VEGF, which inhibits the angiogenesis in malignant tumors. Although Bevacizumab has been approved for first-line use in advanced non-SCLC, the first report has been available for its use in SCLC. In this review, we summarized all available data on the use of Bev in SCLC patients. Finally, future directions are discussed. PMID: 26548757 [Pu...
Source: Current Cancer Drug Targets - November 6, 2015 Category: Cancer & Oncology Authors: Roviello G, Generali D Tags: Curr Cancer Drug Targets Source Type: research

Development of Linker-conjugated Nanosize Lipid Vesicles: A Strategy for Cell Selective Treatment in Breast Cancer.
Abstract Among the various drug delivery devices, nanoliposome is an emerging formulation in the treatment of cancer. Here we developed tamoxifen citrate (TC) loaded nanoliposome conjugated with phosphoethanolamine (PE) by thin film hydration method. Various physicochemical and biopharmaceutical characterization studies such as drug-excipients interaction, surface morphology, energy dispersive X-ray analysis, zeta potential, in vitro drug release, cellular uptake, in vitro cytotoxicity assay and in vivo pharmacokinetic profiles were conducted. TC-loaded nanoliposome (TNL1) and PE-conjugated TC-loaded nanoliposome ...
Source: Current Cancer Drug Targets - November 6, 2015 Category: Cancer & Oncology Authors: Dey NS, Mukherjee B, Maji R, Satapathy BS Tags: Curr Cancer Drug Targets Source Type: research

Targeting ABCB1 and ABCC1 with their specific inhibitor CBT-1 can overcome drug resistance in osteosarcoma.
This study was aimed to estimate the impact on OS drug resistance of a group of ATP binding cassette (ABC) transporters, which in other human tumors have been associated with unresponsiveness to the drugs that represent the backbone of multidrug treatment regimens for OS (doxorubicin, methotrexate, cisplatin). By using a group of 6 drug-sensitive and 20 drug-resistant human OS cell lines, the most relevant transporter which proved to be associated with the degree of drug resistance in OS cells, in addition to ABCB1, was ABCC1. We therefore evaluated the in vitro activity of the orally administrable ABCB1/ABCC1 inhibitor CB...
Source: Current Cancer Drug Targets - November 6, 2015 Category: Cancer & Oncology Authors: Fanelli M, Hattinger CM, Vella S, Tavanti E, Michelacci F, Gudeman B, Barnett D, Picci P, Serra M Tags: Curr Cancer Drug Targets Source Type: research

A new therapeutic era in GCB and ABC Diffuse large B-cell lymphoma molecular subtypes: a cell of origin driven review.
Abstract In the past fifteen years advances in molecular biology have exposed the genetic and physiopathologic heterogeneity of diffuse large B cell lymphoma (DLBCL). Subsets of patients have been identified in which current chemoimmunotherapies may not be as efficacious such as the activated B-cell subtype (ABC). In this review we will make an in-depth review of the differences between the two main DLBCL subsets (germinal center B cell -GCB- and ABC), focusing specifically in their different genetic, active tumoral pathways and pathologic features. We also discuss the bridges that have been built from the bench t...
Source: Current Cancer Drug Targets - October 29, 2015 Category: Cancer & Oncology Authors: Sandoval-Sus JD, Chavez J, Dalia S 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: 26517537 [PubMed - as supp...
Source: Current Cancer Drug Targets - October 29, 2015 Category: Cancer & Oncology Authors: Tsai JL, Lee YM, Pan CY, Yueh-Luen Lee A Tags: Curr Cancer Drug Targets Source Type: research

Indoleamine 2,3-dioxygenase (IDO): Biology and Target in Cancer Immunotherapies.
Abstract Indoleamine 2,3-dioxygenase (IDO) is a heme-containing oxidoreductase that catalyzes the initial and rate-limiting step in the breakdown of non-dietary tryptophan. The biology and immunomodulatory role for IDO is discussed in this review with a focus on its interaction with immune cells and its potential therapeutic target in the clinic. IDO has been revealed to be a central regulator of immune responses in a broad variety of physiological and pathological settings, mostly serving as a multifaceted negative feedback mechanism, to self-regulate immune responses. IDO is considered a therapeutic target in ca...
Source: Current Cancer Drug Targets - October 29, 2015 Category: Cancer & Oncology Authors: Selvan SR, Dowling JP, Kelly WK, Lin J Tags: Curr Cancer Drug Targets Source Type: research

Editorial: Cancer Biomarkers from Bench to Bedside.
PMID: 26452380 [PubMed - in process] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - October 12, 2015 Category: Cancer & Oncology Authors: Gyorffy B Tags: Curr Cancer Drug Targets Source Type: research

Current State of ERG as Biomarker in Prostatic Adenocarcinoma.
Abstract In this review we briefly discuss the possible biomarkers of prostate cancer among them we focus and analyze the relevance of TMPRSS2-ERG fusion gene in line with ERG expression in the diagnosis of prostate cancer. Starting at diagnosis and genetic alterations in prostate carcinomas, we examine the incidence and detection of the most common genetic aberration in this tumor and its protein product as well. We also examined the correlation of clinicopathological factors and prognosis with ERG and the TMPRSS2-ERG fusion oncogene and ERG expression as predictive markers. PMID: 26452381 [PubMed - in proce...
Source: Current Cancer Drug Targets - October 12, 2015 Category: Cancer & Oncology Authors: Acs B, Szarvas T, Szekely N, Nyirady P, Szasz AM Tags: Curr Cancer Drug Targets Source Type: research

The Influence of Host Factors on the Prognosis of Breast Cancer: Stroma and Immune Cell Components as Cancer Biomarkers.
Abstract In this paper, we will review the data on stromal components and immunological parameters in the cancer microenvironment as prognostic and predictive markers in breast cancer. Host immunological response to cancer has gained importance because of recent breakthroughs in immunotherapy. Currently, molecular and clinical subtyping of breast cancer is solely based on the molecular features of the cancer cells without considering the importance of stromal components. There is now clear evidence that infiltrating immune and inflammatory cells influence the biology and clinical course of breast cancer. However, ...
Source: Current Cancer Drug Targets - October 12, 2015 Category: Cancer & Oncology Authors: Karn T, Pusztai L, Rody A, Holtrich U, Becker S Tags: Curr Cancer Drug Targets Source Type: research

A Comprehensive Outline of Trastuzumab Resistance Biomarkers in HER2 Overexpressing Breast Cancer.
Abstract The introduction of trastuzumab for anti-HER2 therapy dramatically changed the clinical outcome for HER2 (ERBB2, neu) positive breast cancer patients. Today, patients eligible for trastuzumab are selected using HER2 expression/amplification status of the primary tumor. However, acquired and inherent resistance to anti-HER2 therapy in these patients poses a significant challenge, and better patient stratification will be needed to improve clinical response. Here, we provide a wide-ranging overview of potential biomarkers capable of stratifying patients regarding their response to trastuzumab. These include...
Source: Current Cancer Drug Targets - October 12, 2015 Category: Cancer & Oncology Authors: Menyhart O, Santarpia L, Gyorffy B Tags: Curr Cancer Drug Targets Source Type: research

Autophagy : Moving Benchside Promises to Patient Bedsides.
Abstract Survival rates of patients with metastatic or recurrent cancers have remained virtually unchanged during the past 30 years. This fact makes the need for new therapeutic options even more urgent. An attractive option would be to target autophagy, an essential quality control process that degrades toxic aggregates, damaged organelles, and signaling proteins, and acts as a tumor suppressor pathway of tumor initiation. Conversely, other fascinating observations suggest that autophagy supports cancer progression, relapse, metastasis, dormancy and resistance to therapy. This review provides an overview of the c...
Source: Current Cancer Drug Targets - October 12, 2015 Category: Cancer & Oncology Authors: Belaid A, Ndiaye PD, Filippakis H, Roux J, Rottinger E, Graba Y, Brest P, Hofman P, Mograbi B Tags: Curr Cancer Drug Targets Source Type: research

Prognostic and Predictive Biomarkers in Colorectal Cancer. From the Preclinical Setting to Clinical Practice.
Abstract Colorectal cancer (CRC) is the second largest cause of cancer mortality in Western countries, mostly due to metastasis. Understanding the natural history and prognostic factors in patients with metastatic CRC (mCRC) is essential for the optimal design of clinical trials. The main prognostic factors currently used in clinical practice are related to tumor behavior (e.g., white blood counts, levels of lactate dehydrogenase, levels of alkaline phosphatase) disease extension (e.g., presence of extrahepatic spread, number of organs affected) and general functional status (e.g., performance status as defined by...
Source: Current Cancer Drug Targets - October 12, 2015 Category: Cancer & Oncology Authors: Maurel J, Postigo A Tags: Curr Cancer Drug Targets Source Type: research

Expression of CDK8 and CDK8-interacting Genes as Potential Biomarkers in Breast Cancer.
Abstract CDK8 and its paralog CDK19, in complex with CCNC, MED12 and MED13, are transcriptional regulators that mediate several carcinogenic pathways and the chemotherapy-induced tumor-supporting paracrine network. Following up on our previous observation that CDK8, CDK19 and CCNC RNA expression is associated with shorter relapse-free survival (RFS) in breast cancer, we now found by immunohistochemical analysis that CDK8/19 protein is overexpressed in invasive ductal carcinomas relative to non-malignant mammary tissues. Meta-analysis of transcriptomic data revealed that higher CDK8 expression is associated with sh...
Source: Current Cancer Drug Targets - October 12, 2015 Category: Cancer & Oncology Authors: Broude EV, Gyorffy B, Chumanevich AA, Chen M, McDermott MS, Shtutman M, Catroppo JF, Roninson IB Tags: Curr Cancer Drug Targets Source Type: research

Extracellular vesicles as novel delivery tools for cancer treatment.
Abstract Extracellular vesicles (EVs) are different types of membrane-derived vesicles that originate from the endosomal pathway or the plasma membrane. These vesicles are used as "carriers" in intercellular communication, and are responsible for the transfer of biological cargo (lipids, proteins, RNA species, and DNA) between different cells. Despite the shortcomings in our knowledge of EV biology, attempts to employ EVs as natural delivery tools for therapeutic purposes have been partly successful in different settings. In this review, we highlight this unique potential of EVs, and discuss previous exa...
Source: Current Cancer Drug Targets - September 23, 2015 Category: Cancer & Oncology Authors: Erkan EP, Saydam O Tags: Curr Cancer Drug Targets Source Type: research

New insights into the molecular resistance mechanisms of chronic myeloid leukemia.
This article reviews new insights into the various molecular resistance mechanisms of CML and discusses treatment strategies based on the targets that have recently been found to play an important role in the molecular mechanisms of resistance. PMID: 26391311 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - September 21, 2015 Category: Cancer & Oncology Authors: Huang R, Kang Q, Liu H, Li Y Tags: Curr Cancer Drug Targets Source Type: research

Persistent GP130/STAT3 signaling contributes to the resistance of doxorubicin, cisplatin, and MEK inhibitor in human rhabdomyosarcoma cells.
Abstract To examine the role of STAT3 plays in human rhabdomyosarcoma cells, we used genetic approaches to either knockdown the expression of STAT3 and the upstream of STAT3, GP130 using shRNA or express constitutive active STAT3 protein. Knockdown the expression of GP130 or STAT3 sensitized cells to anti-cancer drugs doxorubicin, cisplatin, and MEK inhibitor AZD6244. On the other hand, constitutive active STAT3 decreased the sensitivity of cells to those drugs. Additionally, we tested a novel small molecular STAT3 inhibitor LY5 and a GP130 inhibitor bazedoxifene in rhabdomyosarcoma cells. Our data demonstrated th...
Source: Current Cancer Drug Targets - September 15, 2015 Category: Cancer & Oncology Authors: Wu X, Xiao H, Wang R, Liu L, Li C, Lin J Tags: Curr Cancer Drug Targets Source Type: research

Molecular Genetics and Targeted Therapy in Hepatocellular Carcinoma.
Abstract Hepatocellular carcinoma (HCC) is a highly lethal disease, effective and tolerable treatment is urgently needed. In this article, we provide an updated review of the genetic abnormalities and mechanisms that drive carcinogenesis of HCC, and discuss the targeted therapeutics that are being investigated in HCC. Hepatocellular carcinogenesis typically begins with chronic inflammation of hepatocytes that progressively transform into invasive carcinoma. These events are associated with molecular abnormalities and chromosomal alterations. Multiple analyses of HCC have revealed aberrant expression or activity of...
Source: Current Cancer Drug Targets - September 15, 2015 Category: Cancer & Oncology Authors: Marks EI, Yee NS Tags: Curr Cancer Drug Targets Source Type: research

MCY as Therapeutic Target for Embryonal Tumors: Potential and Challenges.
Abstract The MYC family plays essential roles during brain development and their oncogenic deregulation is implicated in the formation of embryonal neural tumors such as medulloblastomas (MB) and neuroblastoma (NB). Amplification of the MYCN is the predominant marker for aggressive NB and correlates with poor prognosis, while c-MYC overexpression is a defining feature of MB subgroups inflected with aggressive biological behavior and increased likelihood of metastasis. Not surprisingly MYC has emerged as an attractive target for pediatric neural cancer therapy. However despite three decades of intensive research in...
Source: Current Cancer Drug Targets - September 15, 2015 Category: Cancer & Oncology Authors: Shalaby T, Grotzer MA Tags: Curr Cancer Drug Targets Source Type: research

Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection.
Abstract The integrity of eukaryotic cellular function depends on molecular and biochemical compartmentalization. The transport of macromolecules between compartments requires specific and energydriven mechanisms. It occurs through a class of transport proteins known as karyopherins, which are divided in three different groups (exportins, importins, and transportins). The ubiquitous exportin Chromosome Region Maintenance 1 (CRM1) is involved in the transport of many proteins and RNA molecules from nucleus to cytoplasm. We have reviewed the available evidence supporting the relevance of CRM1 in the biology of sever...
Source: Current Cancer Drug Targets - September 5, 2015 Category: Cancer & Oncology Authors: Lu C, Figueroa JA, Liu Z, Konala V, Aulakh A, Verma R, Cobos E, Chiriva-Internati M, Gao W Tags: Curr Cancer Drug Targets Source Type: research

Non Steroidal Anti Inflammatory Drugs as Gatekeepers Of Colon Carcinoma Highlight New Scenarios Beyond Cyclooxygenases Inhibition.
Abstract Epidemiological data suggest that Non Steroidal Anti Inflammatory Drugs (NSAIDs) and Cyclooxygenase 2 (COX2) inhibitors (COXibs) can exert chemopreventive and antitumour effects in many human neoplasia. This is particularly true in colon cancer (CC), where the regular assumption of these molecules has been shown to exert chemopreventive and chemotherapeutic effects. Since the late '90s there was a progressive increase of experimental evidence, indicating that in CC the antiproliferative effects of NSAIDs and COXibs could be both dependent and independent from COXs inhibition, and that these effects do not...
Source: Current Cancer Drug Targets - August 26, 2015 Category: Cancer & Oncology Authors: Guarnieri T Tags: Curr Cancer Drug Targets Source Type: research