CXCL3 is a Potential Target for Breast Cancer Metastasis.
Abstract Secreted proteins are an attractive minefield for cancer drug targets. An iTRAQ-based tandem mass spectrometry approach was employed to relatively quantify proteins in the secretomes of four isogenic breast cancer cell lines with increasing metastatic potential. CXCL3 was found to be upregulated in aggressive cancer cells. SiRNA and antibody neutralization studies supported a role of CXCL3 in metastatic processes. Meta-analysis of the mRNA level of CXCL3 in 1881 breast tumors supported a role of CXCL3 in clinical breast cancer. Our results support a functional role of CXCL3 in breast cancer metastasis and...
Source: Current Cancer Drug Targets - March 5, 2014 Category: Cancer & Oncology Authors: See AL, Chong PK, Lu SY, Lim YP Tags: Curr Cancer Drug Targets Source Type: research

Targeting BMP9-Promoted Human Osteosarcoma Growth by Inactivation of Notch Signaling.
Abstract Osteosarcoma (OS) is the most common primary malignancy of bone and usually associated with poor prognosis due to its high incidence of metastasis and chemoresistance. Molecular pathogenesis of OS is poorly understood. We previously showed that OS cells are refractory to BMP9-induced osteogenesis and respond favorably for proliferation and tumor growth. Here we investigate if Notch signaling mediates the BMP9-promoted cell proliferation and tumor growth of human osteosarcoma (OS). We find that the expression of Notch1, Notch2, Notch3, DLL1, JAG1 and JAG2 is readily detected in most of the tested OS cell l...
Source: Current Cancer Drug Targets - March 4, 2014 Category: Cancer & Oncology Authors: Li R, Zhang W, Cui J, Shui W, Yin L, Wang Y, Zhang H, Wang N, Wu N, Nan G, Chen X, Wen S, Deng F, Zhang H, Zhou G, Liao Z, Zhang J, Zhang Q, Yan Z, Liu W, Zhang Z, Ye J, Deng Y, Luu HH, Haydon RC, He TC, Deng ZL Tags: Curr Cancer Drug Targets Source Type: research

Novel Insights into the Role of MicroRNA in Lung Cancer Resistance to Treatment and Targeted Therapy.
Abstract Lung cancer is one of the most common malignant tumors and is the leading cause of cancer mortality worldwide. However, drug resistance induced by chemotherapeutants to lung cancer cells is the primary issue during the chemotherapy of lung cancer. Many mechanisms such as the changes of drug metabolism related genes and signal pathways are involved in the chemoresistance. MicroRNAs (miRNAs) are a class of endogenetic, non-coding, short-chain and small RNAs that regulate cell growth, apoptosis and signal transduction. There are growing numbers of evidence suggesting that miRNA polymorphisms associate with d...
Source: Current Cancer Drug Targets - March 4, 2014 Category: Cancer & Oncology Authors: Gong Z, Yang J, Li J, Yang L, Le Y, Wang S, Lin HK Tags: Curr Cancer Drug Targets Source Type: research

Gemcitabine Resistance is Associated with Epithelial-Mesenchymal Transition and Induction of HIF-1 in Pancreatic Cancer Cells.
Abstract Pancreatic cancer is one of highly aggressive malignant diseases worldwide. To achieve the better treatment outcome of pancreatic cancer, in the current study we explore the underlying molecular mechanism of drug resistance in pancreatic cancer cells. We found that resistance to gemcitabine is associated with epithelial-mesenchymal transition (EMT) phenotype in a panel of pancreatic cancer cell lines. Notably, gemcitabine-resistant pancreatic cancer cells acquired EMT phenotype. Moreover, gemcitabine-resistant cells have increased migration and invasion activities. Furthermore, we observed the high expres...
Source: Current Cancer Drug Targets - February 25, 2014 Category: Cancer & Oncology Authors: Wang R, Cheng L, Xia J, Wang Z, Wu Q, Wang Z Tags: Curr Cancer Drug Targets Source Type: research

Heparanase As A Target In Cancer Therapy.
Abstract Heparanase is the unique and specific functional endoglycosidase capable of cleaving heparansulfate (HS) chains. It exerts its enzymatic activity catalyzing the cleavage of the β (1,4)-glycosidic bond between glucuronic acid and glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion. A pro-metastatic and pro-angiogenic role for this enzyme has been widely demonstrated in many primary human tumours since ...
Source: Current Cancer Drug Targets - February 24, 2014 Category: Cancer & Oncology Authors: Masola V, Secchi MF, Gambaro G, Onisto M Tags: Curr Cancer Drug Targets Source Type: research

Cetuximab Inhibits Gastric Cancer Growth in vivo, Independent of KRAS Status.
In conclusion, KRAS (G→A) mutation does not affect in vivo anti-cancer efficacy of Cetuximab. PMID: 24467518 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - January 27, 2014 Category: Cancer & Oncology Authors: Shi M, Shi H, Ji J, Cai Q, Chen X, Yu Y, Liu B, Zhu Z, Zhang J Tags: Curr Cancer Drug Targets Source Type: research

Pleiotropic Role of HSF in Neoplastic Transformation.
Abstract HSF (Heat Shock transcription Factor 1) is the main transcription factor activated in response to proteotoxic stress. Once activated, it induces an expression of heat shock proteins (HSPs) which enables cells to survive in suboptimal conditions. HSF could be also activated by altered kinase signaling characteristic for cancer cells, which is a probable reason for its high activity found in a broad range of tumors. There is rapidly growing evidence that HSF supports tumor initiation and growth, as well as metastasis and angiogenesis. It also modulates the sensitivity of cancer cells to therapy. Functions o...
Source: Current Cancer Drug Targets - January 22, 2014 Category: Cancer & Oncology Authors: Vydra N, Toma A, Widlak W Tags: Curr Cancer Drug Targets Source Type: research

Molecular Targeted Approaches to Cancer Therapy and Prevention using Chalcones.
Abstract There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcone...
Source: Current Cancer Drug Targets - January 22, 2014 Category: Cancer & Oncology Authors: Jandial DD, Blair CA, Zhang S, Krill LS, Yan-Bing Z, Zi X Tags: Curr Cancer Drug Targets Source Type: research

BRAF Inhibitor Therapy for Melanoma, Thyroid and Colorectal Cancers: Development of Resistance and Future Prospects.
Abstract BRAF is a major oncoprotein and oncogenic mutations in BRAF are found in a significant number of cancers, including melanoma, thyroid cancer, colorectal cancer and others. Consequently, BRAF inhibitors have been developed as treatment options for cancers with BRAF mutations which have shown some success in improving patient outcomes in clinical trials. Development of resistance to BRAF kinase inhibitors is common, however, and overcoming this resistance is an area of significant concern for clinicians, patients and researchers alike. In this review, we identify the mechanisms of BRAF kinase inhibitor resi...
Source: Current Cancer Drug Targets - January 21, 2014 Category: Cancer & Oncology Authors: Rahman AU, Salajegheh A, Smith RA, Lam AK Tags: Curr Cancer Drug Targets Source Type: research

Novel Anticancer Strategy Aimed at Targeting Shelterin Complexes by the Induction of Structural Changes in Telomeric DNA: Hitting Two Birds with One Stone.
Abstract The ends of chromosomes in mammals are composed of telomeric DNA containing TTAGGG repeats, which bind specific proteins called shelterins. This telomeric DNA together with shelterins form a cap that protects the ends of chromosomes from being recognized as sites of DNA damage and from chromosomal fusions. Many very successful antitumor drugs used in the treatment of cancer patients bind to DNA, some of them with a prominent sequence specificity that leads to changes in DNA structure and integrity. We propose a new target for antitumor drugs where small molecule ligands can bind to telomeric DNA and induc...
Source: Current Cancer Drug Targets - January 20, 2014 Category: Cancer & Oncology Authors: Bidzinska J, Baginski M, Skladanowski A Tags: Curr Cancer Drug Targets Source Type: research

Cationic Liposome Mediated Delivery of FUS1 and hIL-12 Coexpression Plasmid Demonstrates Enhanced Activity against Human Lung Cancer.
Abstract FUS1 is one of the most important tumor suppressor genes in lung cancer, as well as an important immunomodulatory molecule. Interleukin (IL)-12 has attracted considerable interest as a potential anti-tumor cytokine. Cationic liposome has been shown to effectively deliver therapeutic genes to the lungs and control metastatic lung tumors when administered intravenously. Here we evaluated the enhanced efficacy of cationic liposome-mediated delivery of FUS1 and human IL (hIL)-12 eukaryotic coexpression plasmid (pVITRO2-FUS1-hIL-12) against the human lung cancer in HuPBL-NOD/SCID mice model by local and system...
Source: Current Cancer Drug Targets - January 12, 2014 Category: Cancer & Oncology Authors: Ren J, Yu C, Wu S, Peng F, Jiang Q, Zhang X, Zhong G, Shi H, Chen X, Su X, Luo X, Zhu W, Wei Y Tags: Curr Cancer Drug Targets Source Type: research

Anticancer Effect of a Curcumin Derivative B63: ROS Production and Mitochondrial Dysfunction.
Abstract Curcumin, a polyphenol isolated from the plant Curcuma longa, displays chemotherapeutic and chemopreventive effects in diverse cancers, including colorectal cancer. A mono-carbonyl analogue B63 was synthesized through several chemical modifications of the basic structure of curcumin to increase its biological activity and bioavailability. In vitro assays showed potent anti- proliferative effects of B63 on colon cancer cells (about 2 fold more effective than curcumin based on IC50). B63 treatment also induced significant necrosis, apoptosis and S phase cell cycle arrest in SW620 colon cancer cells. The pro...
Source: Current Cancer Drug Targets - November 25, 2013 Category: Cancer & Oncology Authors: Zheng A, Li H, Wang X, Feng Z, Xu J, Cao K, Zhou B Tags: Curr Cancer Drug Targets Source Type: research

The Role Of E-Cadherin Down-Regulation In Oral Cancer: Cdh1 Gene Expression And Epigenetic Blockage.
Conclusion: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR. PMID: 24274398 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - November 25, 2013 Category: Cancer & Oncology Authors: Pannone G, Santoro A, Feola A, Bufo P, Papagerakis P, Lo Muzio L, Staibano S, Ionna F, Longo F, Franco R, Aquino G, Contaldo M, De Maria S, Serpico R, De Rosa A, Rubini C, Papagerakis S, Giovane A, Tombolini V, Giordano A, Caraglia M, Di Domenico M Tags: Curr Cancer Drug Targets Source Type: research

PIM1 Kinase as a Target in Prostate Cancer: Roles in Tumorigenesis, Castration Resistance, and Docetaxel Resistance.
Abstract PIM1 kinase is a serine/threonine kinase that has been shown to be overexpressed in multiple human malignancies, including prostate cancer. PIM1 phosphorylates multiple cellular substrates to inhibit apoptosis and promote cell cycle progression. Increased PIM1 can also facilitate genomic instability to promote neoplastic processes. PIM1 kinase is overexpressed in high-grade prostate intraepithelial neoplasia and in prostate cancer compared to normal prostatic tissue and benign prostate hyperplasia. Elevated PIM1 levels have been shown to be the direct result of oncogenic fusion proteins and active signal ...
Source: Current Cancer Drug Targets - November 25, 2013 Category: Cancer & Oncology Authors: Holder SL, Abdulkadir SA Tags: Curr Cancer Drug Targets Source Type: research

Suppression of NF-κB signaling and P-glycoprotein Function by Gambogic Acid Synergistically Potentiates Adriamycin -induced Apoptosis in Lung Cancer.
Suppression of NF-κB signaling and P-glycoprotein Function by Gambogic Acid Synergistically Potentiates Adriamycin -induced Apoptosis in Lung Cancer. Curr Cancer Drug Targets. 2013 Nov 12; Authors: Wang LH, Yang JY, Yang SN, Li Y, Ping GF, Hou Y, Cui W, Wang ZZ, Xiao W, Wu CF Abstract Gambogic acid (GA) has been approved by the Chinese Food and Drug Administration for the treatment of lung cancer in clinical trials. However, whether GA has chemosensitizing properties when combined with other chemotherapy agents in the treatment of lung cancer is not known. Here we investigated the effects of GA combi...
Source: Current Cancer Drug Targets - November 12, 2013 Category: Cancer & Oncology Authors: Wang LH, Yang JY, Yang SN, Li Y, Ping GF, Hou Y, Cui W, Wang ZZ, Xiao W, Wu CF Tags: Curr Cancer Drug Targets Source Type: research

Resistance to Peloruside A and Laulimalide: Functional Significance of Acquired βI-Tubulin Mutations at Sites Important for Drug-Tubulin Binding.
This study provides the first direct evidence that A296 and R306 of βI-tubulin are important determinants of the PLA and LAU response in cancer cells. PMID: 24245693 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - November 12, 2013 Category: Cancer & Oncology Authors: Kanakkanthara A, Eras J, Northcote PT, Cabral F, Miller JH Tags: Curr Cancer Drug Targets Source Type: research

Activity of Drug-loaded Tumor-Penetrating Microparticles In Peritoneal Pancreatic Tumors.
Abstract Intraperitoneal (IP) chemotherapy confers significant survival benefits in cancer patients. However, several problems, including local toxicity and ineffectiveness against bulky tumors, have prohibited it from becoming a standard of care. We have developed drug-loaded, polymeric tumor-penetrating microparticles (TPM) to address these problems. Initial studies showed that TPM provides tumor-selective delivery and is effective against ovarian SKOV3 tumors of relatively small size (
Source: Current Cancer Drug Targets - November 4, 2013 Category: Cancer & Oncology Authors: Lu Z, Tsai M, Wang J, Cole DJ, Wientjes MG, Au JL Tags: Curr Cancer Drug Targets Source Type: research

Cyclophilin A as a Target of Cisplatin Chemosensitizers.
Abstract Platinum-based chemotherapeutics are the mainstay of treatment of a range of tumors achieving high response rates but limited in the course of disease by appearance of drug resistance. Tumor cells respond with reduced uptake and increased intracellular inactivation of the drugs, as well as increased DNA repair and general resistance to chemotherapy-induced cell death. Cisplatin is known to induce expression of cyclophilins, a group of proteins that have peptidyl-prolyl cis-trans isomerase (PPIase) and molecular chaperone activities, as stress response. Cyclophilin A (CypA) and other members of this family...
Source: Current Cancer Drug Targets - November 4, 2013 Category: Cancer & Oncology Authors: Hamilton G Tags: Curr Cancer Drug Targets Source Type: research

A Water Soluble Parthenolide, Dimethylaminoparthenolide (DMAPT), Suppresses Lung Tumorigenesis in Vitro and in Vivo and Downregulates the STAT3 Signaling Pathway.
Abstract Lung cancer is the most fatal cancer and development of agents that suppress lung tumorigenesis is a crucial strategy to reduce mortality related to this disease. In the present study, we showed, using an in vitro model of lung tumorigenesis, that dimethylamino-parthenolide (DMAPT), a water soluble parthenolide analog, selectively inhibited the growth and survival of premalignant and malignant cells with minimal effects on parental immortalized cells. These effects were paralleled by suppression of pSTAT3, Mcl-1 and cyclin D1 and PARP cleavage, suggesting that that the anti-proliferative and apoptotic eff...
Source: Current Cancer Drug Targets - November 4, 2013 Category: Cancer & Oncology Authors: Song JM, Qian X, Upadhyayya P, Hong KH, Kassie F Tags: Curr Cancer Drug Targets Source Type: research

Role of Inflammation-Associated Microenvironment in Tumorigenesis and Metastasis.
Abstract The tumor microenvironment contributes to every aspect of carcinogenesis and therefore offers promising targets for cancer therapy. Compared to chemotherapy alone, targeting tumor cells as well as key components of the tumor microenvironment significantly improve the clinical outcomes of patients. A better understanding of the interaction between tumor cells and the microenvironment could provide new therapeutic options and accelerate the development of novel anti-cancer drugs. In this review, we first defined the tumor microenvironment and then discussed the role of the tumor microenvironment in the init...
Source: Current Cancer Drug Targets - November 4, 2013 Category: Cancer & Oncology Authors: Gao F, Liang B, Reddy ST, Farias-Eisner R, Su X Tags: Curr Cancer Drug Targets Source Type: research

Protein Phosphatase 1 and its Complexes in Carcinogenesis.
Abstract Understanding the molecular mechanisms and the signaling pathways that underlie the pathology of cancer progression is crucial for the development of novel diagnostic and therapeutic tools. A major common mechanism used by cells to regulate intracellular signal transduction pathways is reversible protein phosphorylation which results in profound changes in cellular responses. This mechanism relies on the coordinated action of two families of proteins: protein kinases and protein phosphatases. Interestingly, there are 3 to 5 times fewer phosphatases than kinases, suggesting that the specificity of substrat...
Source: Current Cancer Drug Targets - November 3, 2013 Category: Cancer & Oncology Authors: Figueiredo J, Cruz E Silva OA, Fardilha M Tags: Curr Cancer Drug Targets Source Type: research

Decoding the Knots of Initiation of Oncogenic Epithelial-Mesenchymal Transition in Tumor Progression.
Abstract Oncogenic epithelial-mesenchymal transition (oncEMT) plays important roles in the genesis of cancer stem cells (CSCs), malignant tumor initiation and progression, cancer metastasis, and drug resistance. Although the role of oncEMT in tumorigenesis has recently been extensively studied, the initiation of oncEMT is not clearly understood, and its mechanisms of action are still unknown. Emerging evidence suggests that oncEMT is a complex process, which involves multiple endogenous and exogenous factors. Overexpression of several oncogenes and reprogramming factors in precancerous and cancerous cells, includi...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Guo P, Gao A, Zhang G, Han H, Zhou Q Tags: Curr Cancer Drug Targets Source Type: research

Regulation of EMT by KLF4 in Gastrointestinal Cancer.
Abstract Gastrointestinal (GI) cancer is characterized by its aggressiveness, but the underlying mechanism is not fully understood. Studies reveal that epithelial to mesenchymal transition (EMT), which is regulated by a series of transcription factors and signaling pathways, is strongly associated with GI cancer cell proliferation, invasion and metastasis. In essential, EMT is a product of crosstalk between signaling pathways. Krüppel-like factor 4 (KLF4), a zinc finger-type transcription factor, is decreased or lost in most GI cancers. By transcriptional regulating its downstream target genes, KLF4 plays imp...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Cui J, Shi M, Quan M, Xie K Tags: Curr Cancer Drug Targets Source Type: research

Epigenetic Regulation of Epithelial to Mesenchymal Transition.
Abstract Epithelial-mesenchymal transition (EMT)is a vital process implemented inembryo development, organ fibrosis, and cancer metastasis.Several transcriptional factors and signaling pathways impinge on the transcriptional program of the cell, leading to the change of cell phenotype without alteration of genotype.Accumulating evidence suggests that epigenetic mechanisms play important roles in inducing EMT and orchest rating the heredity and reversibility of EMT. In this review, we discuss how DNA methylation, histone modifications, and microRNAs (miRNAs) act in a concertedmanner to regulate EMT. 'Epigenetic the...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Huangyang P, Shang Y Tags: Curr Cancer Drug Targets Source Type: research

The Role of Snail in EMT and Tumorigenesis.
Abstract Epithelial-mesenchymal transition (EMT) is a highly conserved process in which polarized, immobile epithelial cells lose tight junctions, associated adherence, and become migratory mesenchymal cells. Several transcription factors, including the Snail/Slug family, Twist, δEF1/ZEB1, SIP1/ZEB2 and E12/E47 respond to microenvironmental stimuli and function as molecular switches for the EMT program. Snail is a zinc-finger transcriptional repressor controlling EMT during embryogenesis and tumor progression. Through its N-terminal SNAG domain, Snail interacts with several co-repressors and epigenetic remod...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Wang Y, Shi J, Chai K, Ying X, Zhou BP Tags: Curr Cancer Drug Targets Source Type: research

Regulation of EMT by Notch Signaling Pathway in Tumor Progression.
Abstract Notch signaling pathway has been reported to play critical roles in the development and progression of human cancers because Notch signaling pathway is critically involved in many cellular processes including cell proliferation, survival, apoptosis, migration, invasion, angiogenesis, and metastasis. Emerging evidence suggests that Notch regulates EMT (Epithelial-to-Mesenchymal Transition), leading to tumor invasion and metastasis. Thus, this mini-review is focused on discussing the novel role of Notch signaling pathway in the regulation of EMT. Moreover, we summarized that Notch signaling pathway could be...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Li Y, Ma J, Qian X, Wu Q, Xia J, Miele L, Sarkar FH, Wang Z Tags: Curr Cancer Drug Targets Source Type: research

Emerging Role of Mucins for Epithelial to Mesenchymal Transition.
Abstract Epithelial to mesenchymal transition (EMT) is an important and complex phenomenon that determines the aggressiveness of cancer cells. The morphological transformation of cancerous cells is accompanied by various cellular processes such as alterations in cell- cell adhesion, cell matrix degradation, down regulation of epithelial marker E-cadherin and upregulation of mesenchymal markers N-cadherin and Vimentin. Besides these markers several other important tumor antigens/mucins are also involved in EMT process. Mainly high molecular weight glycoproteins such as mucins molecules (MUC1, MUC4 and MUC16) are pl...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Ponnusamy MP, Seshacharyulu P, Lakshmanan I, Vaz AP, Chugh S, Batra SK Tags: Curr Cancer Drug Targets Source Type: research

MicroRNAs as Critical Regulators Involved in Regulating Epithelial-Mesenchymal Transition.
Abstract The epithelial-mesenchymal transition (EMT) is a fundamental biological process that is involved in normal embryogenesis, would healing, and tissue repair, as well as numerous pathologies, including organ fibrosis, malignant transformation, and cancer progression. Both transcriptional and post-transcriptional regulatory mechanisms contribute to a complex and tightly controlled regulatory network during the EMT process, and a growing body of evidence now demonstrates that microRNAs (miRNAs) are crucial regulators of this network. miRNAs are a class of small non-coding RNAs that regulate gene expression thr...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Zhao X, Lu Y, Nie Y, Fan D Tags: Curr Cancer Drug Targets Source Type: research

Regulation of Mesenchymal Phenotype by MicroRNAs in Cancer.
Abstract Epithelial-mesenchymal transition (EMT)is a developmental process that converts epithelial cells into migratory and invasive cells. This process also playsan important role in cancer progression and metastasis by enabling tumor cells to leave primary sites. EMT is regulated by complex transcription networks and post-transcriptional modulators. MicroRNAs are single-stranded noncoding RNAs that represent a novel class of gene regulators. It has been shown that microRNAs are critical regulators of EMT process. The molecular mechanisms of EMT modulation by microRNAs include the suppression of transcription fa...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Yan J, Gumireddy K, Li A, Huang Q Tags: Curr Cancer Drug Targets Source Type: research

Roles of Epithelial-mesenchymal Transition in Cancer Drug Resistance.
Abstract Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer. Poor responses to drug treatment can result in metastasis, cancer dissemination and death. Recently, the epithelial-mesenchymal transition (EMT) has been found to play a critical role in cancer drug resistance, but the nature of this intrinsic link remains unclear. This review summarizes recent advances in the understanding of drug resistance and focuses especially on the association between EMT and drug resistance. We discuss the roles of EMT in regulating drug resistance across different types of cancer, focusing ...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Shang Y, Cai X, Fan D Tags: Curr Cancer Drug Targets Source Type: research

Unveiling the role of Nuclear Transport in Epithelial-to-Mesenchymal Transition.
Abstract Epithelial-to-Mesenchymal transition (EMT) is a phenomenon in which cells loose their polarity, undergo morphological changes from epithelial to mesenchymal thereby achieving plasticity that confers an invasive and metastatic behavior. A large number of signaling molecules (Wnt/β-Catenin, TGF-β, notch, EGF, HGF and hypoxia) have been implicated in the EMT process. The EMT signaling molecules are localized either extracellularly, in the cytosol, or in the nucleus. The Wnt, TGF-β, notch, EGF and HGF signaling initiate from receptors on the cell surface through the cytoplasm and ultimately to ...
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Azmi AS Tags: Curr Cancer Drug Targets Source Type: research

EDITORIAL: Emerging Roles of Epithelial-to-Mesenchymal Transition in Tumorigenesis.
PMID: 24168193 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - October 29, 2013 Category: Cancer & Oncology Authors: Wang Z Tags: Curr Cancer Drug Targets Source Type: research

Stem cell transplantation for chronic myeloid leukemia (cml) in the tyrosine kinase inhibitor era.
In conclusion, allogeneic SCT remains a therapeutic option for selected patients with CML and is currently being integrated with the use of TKIs both before and after transplantation. PMID: 24041269 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - September 16, 2013 Category: Cancer & Oncology Authors: Bacigalupo A Tags: Curr Cancer Drug Targets Source Type: research

Protein Phosphatase 2A as a Potential Target for Treatment of Adult T Cell Leukemia.
Abstract The aim of this study was to establish the role of serine/threonine protein phosphatase 2A (PP2A) in the survival of leukemic cells from patients with adult T cell leukemia (ATL), associated with human T cell leukemia virus type 1 (HTLV-1). In HTLV-1-infected T cell lines and ATL cells, okadaic acid (OkA), a potent PP2A inhibitor, induced decrease in cell viability and G1 cell cycle arrest by decreasing the expression levels of of cyclin D2, cyclin-dependent kinase 4 and cyclin-dependent kinase 6, phosphorylation of pRb, and upregulation of p21, p27 and GADD45a. OkA-induced apoptosis was also due to the s...
Source: Current Cancer Drug Targets - September 5, 2013 Category: Cancer & Oncology Authors: Mori N, Ishikawa C, Uchihara JN, Yasumoto T Tags: Curr Cancer Drug Targets Source Type: research

Significance of Prion and Prion-Like Proteins in Cancer Development, Progression and Multi-Drug Resistance.
Abstract Prions are renowned for their role in neurodegenerative diseases in humans and animals. These are manifested as transmissible spongiform encephalopathies (TSEs) that result from the conversion of the normal glycosylphosphatidylinositol (GPI) anchored cellular prion protein (PrPc) to a misfolded, aggregated and pathogenic form, prion protein scrapie (PrPSc) via a post-translational process followed by the accumulation of PrPSc within the central nervous system. New research in this area has demonstrated that PrP is over-expressed in a variety of cancers including gastric, pancreatic and breast cancers, aff...
Source: Current Cancer Drug Targets - September 5, 2013 Category: Cancer & Oncology Authors: Hinton C, Antony H, Hashimi SM, Munn A, Wei MQ Tags: Curr Cancer Drug Targets Source Type: research

Editorial:Chronic Myeloid Leukemia: Reaching For the Cure.
PMID: 23957630 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - August 16, 2013 Category: Cancer & Oncology Authors: Nencioni A, Cea M, Montecucco F, Gobbi M, Patrone F Tags: Curr Cancer Drug Targets Source Type: research

Treatment of Chronic Myeloid Leukemia elderly patients in the Tyrosine Kinase Inhibitor era.
ina F Abstract The prevalence of chronic myeloid leukemia (CML) is expected to double in the next 15 years. The introduction of imatinib significantly changed the prognosis of CML, challenging the concept of a fatal disease. Now-days, imatinib, nilotinib and dasatinib are registered for first-line treatment of CML patients in chronic phase (CP). Considering elderly patients, the most extensively studied TKI is imatinib, that induces a rate of cytogenetic and molecular responses comparable between the younger and the elderly patients. Once a CCgR with imatinib is achieved, the probability to be alive and disease fr...
Source: Current Cancer Drug Targets - August 6, 2013 Category: Cancer & Oncology Authors: Russo D, Malagola M, Skert C, Filì C, Bergonzi C, Cattina F Tags: Curr Cancer Drug Targets Source Type: research

Use of Single Nucleotide Polymorphism Array Technology to Improve the Identification of Chromosomal Lesions in Leukemia.
Abstract Acute leukemias are characterized by recurring chromosomal and genetic abnormalities that disrupt normal development and drive aberrant cell proliferation and survival. Identification of these abnormalities plays important role in diagnosis, risk assessment and patient classification. Until the last decade methods to detect these aberrations have included genome wide approaches, such as conventional cytogenetics, but with a low sensitivity (5-10%), or gene candidate approaches, such as fluorescent in situ hybridization, having a greater sensitivity but being limited to only known regions of the genome. Si...
Source: Current Cancer Drug Targets - August 6, 2013 Category: Cancer & Oncology Authors: Iacobucci I, Lonetti A, Papayannidis C, Martinelli G Tags: Curr Cancer Drug Targets Source Type: research

Autophagy in Chronic Myeloid Leukaemia: Stem Cell Survival and Implication in Therapy.
Abstract The insensitivity of Chronic Myeloid Leukaemia (CML) stem cells to Tyrosine Kinase Inhibitor (TKI) treatment is now believed to be the main reason for disease persistence experienced in patients. It has been shown that autophagy, an evolutionarily conserved catabolic process that involves degradation of unnecessary or harmful cellular components via lysosomes, is induced following TKI treatment in CML cells. Of clinical importance, autophagy inhibition, using the anti-malarial drug hydroxychloroquine (HCQ), sensitised CML cells, including primitive CML stem cells, to TKI treatment. In this review we discu...
Source: Current Cancer Drug Targets - August 6, 2013 Category: Cancer & Oncology Authors: Helgason GV, Mukhopadhyay A, Karvela M, Salomoni P, Calabretta B, Holyoake TL Tags: Curr Cancer Drug Targets Source Type: research

Alternative Splicing in Chronic Myeloid Leukemia (CML): A Novel Therapeutic Target?
Abstract Although the imatinib based therapy of chronic myeloid leukemia (CML) represents a triumph of medicine, not all patients with CML benefit from this drug due to the development of resistance and intolerance. The interruption of imatinib treatment is often followed by clinical relapse, suggesting a failure in the killing of residual leukaemic stem cells. There is need to identify alternative selective molecular targets for this disease and develop more effective therapeutic approaches. Alternative pre-mRNA splicing (AS) is an epigenetic process that greatly diversifies the repertoire of the transcriptome. A...
Source: Current Cancer Drug Targets - July 30, 2013 Category: Cancer & Oncology Authors: Adamia S, Pilarski PM, Natan MB, Stone RM, Griffin JD Tags: Curr Cancer Drug Targets Source Type: research

Advances in Immunotherapy of Chronic Myeloid Leukemia CML.
Abstract Tyrosine kinase inhibitors induce sustained disease remissions in chronic myeloid leukemia by exploiting the addiction of this type of leukemia to the activity of the fusion oncogene BCR-ABL. However, these agents fail to eradicate CML stem cells which are ultimately responsible for disease relapses upon treatment discontinuation. Evidence that the immune system can effectively reject CML stem cells potentially leading to patient cure is provided by the experience with patients receiving allogeneic bone marrow transplantations. Compelling evidence indicates that more modern, antigen-specific immunotherape...
Source: Current Cancer Drug Targets - July 30, 2013 Category: Cancer & Oncology Authors: Erika Held SA, Heine A, Mayer KT, Kapelle M, Wolf DG, Brossart P Tags: Curr Cancer Drug Targets Source Type: research

New insights into biology of chronic myeloid leukemia: implications in therapy.
NEW INSIGHTS INTO BIOLOGY OF CHRONIC MYELOID LEUKEMIA: IMPLICATIONS IN THERAPY. Curr Cancer Drug Targets. 2013 Jul 30; Authors: Cea M, Cagnetta A, Nencioni A, Gobbi M, Patrone F Abstract Over the past decades the prognosis of patients with Chronic Myeloid Leukemia (CML) has radically changed due to groundbreaking scientific and translational studies that have revealed the biologic basis of such a hematologic malignancy. These studies have led to the rapid development of many BCR-ABL specific tyrosine kinase inhibitors (TKIs), such as Imatinib, Nilotinib and Dasatinib, which have improved 10-years survival ...
Source: Current Cancer Drug Targets - July 30, 2013 Category: Cancer & Oncology Authors: Cea M, Cagnetta A, Nencioni A, Gobbi M, Patrone F Tags: Curr Cancer Drug Targets Source Type: research

Evaluating Treatment Response of Chronic Myeloid Leukemia: Emerging Science and Technology.
Abstract Chronic myeloid leukemia (CML) is a hematological disease that represents 20% of all adult leukemias. The biologic and clinical advances obtained in CML are the most successful examples of translational medicine, in which identification of the fusion oncogene BCR-ABL has allowed the discovery of small molecule inhibitors of its tyrosine kinase activity which, in turn, have literally revolutionized the treatment of such malignancy. However, large part of a successful clinical management of CML relies on appropriate diagnosis, molecular monitoring and identification of mutations potentially leading to drug ...
Source: Current Cancer Drug Targets - July 30, 2013 Category: Cancer & Oncology Authors: Garuti A, Cagnetta A, Marani C, Miglino M, Cea M, Rocco I, Palermo C, Fugazza G, Cirmena G, Colombo N, Grasso R, Nencioni A, Gobbi M, Patrone F Tags: Curr Cancer Drug Targets Source Type: research

Small Molecule Inhibitors of Multidrug Resistance Gene (MDR1) Expression: Preclinical Evaluation and Mechanisms of Action.
Abstract The resistance of tumors to a number of structurally and functionally unrelated chemotherapeutic drugs has been a major obstacle for successful cancer chemotherapy. An important mechanism leading to multidrug resistance (MDR) is the overexpression of the 170 kDa P-glycoprotein (P-gp), which is a member of the ATP-binding cassette (ABC) superfamily of membrane transporters, encoded by the MDR1 gene. Aiming to overcome MDR and due to the clinical failure of P-gp inhibitors, downregulation of MDR1 expression by small molecules has been studied as a possible cancer adjuvant chemotherapy. Here we review the cu...
Source: Current Cancer Drug Targets - July 22, 2013 Category: Cancer & Oncology Authors: Santos SA, Paulo A Tags: Curr Cancer Drug Targets Source Type: research

β-Catenin Knockdown in Liver Tumor Cells by a Cell Permeable Gamma Guanidine-based Peptide Nucleic Acid.
β-Catenin Knockdown in Liver Tumor Cells by a Cell Permeable Gamma Guanidine-based Peptide Nucleic Acid. Curr Cancer Drug Targets. 2013 Jul 1; Authors: Delgado E, Bahal R, Yang J, Lee JM, Ly DH, Monga SP Abstract Hepatocellular cancer (HCC) is the third cause of death by cancer worldwide. In the current study we target β-catenin, an oncogene mutated and constitutively active in 20-30% of HCCs, via a novel, cell permeable gamma guanidine-based peptide nucleic acid (γGPNA) antisense oligonucleotide designed against either the transcription or the translation start site of the human β-cat...
Source: Current Cancer Drug Targets - July 1, 2013 Category: Cancer & Oncology Authors: Delgado E, Bahal R, Yang J, Lee JM, Ly DH, Monga SP Tags: Curr Cancer Drug Targets Source Type: research

Anti-cancer Molecular Targets of Natural Products.
Abstract PMID: 23802843 [PubMed - as supplied by publisher] (Source: Current Cancer Drug Targets)
Source: Current Cancer Drug Targets - June 27, 2013 Category: Cancer & Oncology Authors: Zi X, Zhang R Tags: Curr Cancer Drug Targets Source Type: research

Optimizing Outcomes Following Allogeneic Hematopoietic Progenitor Cell Transplantation in AML: The Role of Hypomethylating Agents.
Abstract Aberrant DNA methylation is a key pathological mechanism in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and provides rationale for the clinical development of hypomethylating agents (HMAs) for the treatment of these diseases. One HMA, azacitidine (Vidaza®, Celgene Corp.), has demonstrated improved survival versus conventional care regimens in patients with intermediate-2/high-risk MDS and AML (20-30% blasts) and has a favorable tolerability profile. Emerging evidence indicates that azacitidine can have an immunomodulatory effect by, for example, increasing functional regulatory T...
Source: Current Cancer Drug Targets - May 22, 2013 Category: Cancer & Oncology Authors: Martino M, Fedele R, Moscato T, Ronco F Tags: Curr Cancer Drug Targets Source Type: research

Histone Lysine-Specific Methyltransferases and Demethylases in Carcinogenesis: New Targets for Cancer Therapy and Prevention.
Abstract Aberrant histone lysine methylation that is controlled by histone lysine methyltransferases (KMTs) and demethylases (KDMs) plays significant roles in carcinogenesis. Infections by tumor viruses or parasites and exposures to chemical carcinogens can modify the process of histone lysine methylation. Many KMTs and KDMs contribute to malignant transformation by regulating the expression of human telomerase reverse transcriptase (hTERT), forming a fused gene, interacting with proto-oncogenes or being up-regulated in cancer cells. In addition, histone lysine methylation participates in tumor suppressor gene ina...
Source: Current Cancer Drug Targets - May 22, 2013 Category: Cancer & Oncology Authors: Tian X, Zhang S, Liu HM, Zhang YB, Blair CA, Mercola D, Sassone-Corsi P, Zi X Tags: Curr Cancer Drug Targets Source Type: research

Targeting Hypoxia for Sensitization of Tumors to Radio-and Chemo-therapy.
Abstract The heterogeneous distribution of hypoxic regions within solid tumors renders them refractive to chemo- and radio-therapies and contributes positively to tumor invasion and metastasis. Moreover, hypoxia favors the enrichment of cancer stem cells by interacting with differentiation signals via the maintenance of stem cell properties of undifferentiated cells or via the induction of cellular dedifferentiation. The discovery of the hypoxia inducible factor 1alpha (HIF-1α) has led to the current extensive interest in the signal molecules related to tumor hypoxia and the major regulatory pathways that co...
Source: Current Cancer Drug Targets - May 17, 2013 Category: Cancer & Oncology Authors: Ghattass K, Assah R, El-Sabban M, Gali-Muhtasib H Tags: Curr Cancer Drug Targets Source Type: research

Inhibition of Hedgehog/Gli Signaling by Botanicals: A Review of Compounds with Potential Hedgehog Pathway Inhibitory Activities.
Abstract The hedgehog (Hh) signaling pathway is an important therapeutic target in cancer; involvement of the Hh pathway has been shown in a variety of cancers including basal cell carcinoma, medulloblastoma, leukemia, and gastrointestinal, breast, prostate, lung, and pancreatic cancers.Currently, several Hh pathway inhibitory drugs are in clinical development, and the FDA recently approved Erivedge (vismodegib) from Curis/Genentech.These new drugs are effective in many, but not all patients. In fact there are documented reports of tumors developing mutations that confer resistance to the drugs.This highlights the...
Source: Current Cancer Drug Targets - May 9, 2013 Category: Cancer & Oncology Authors: Drenkhahn SK, Jackson GA, Slusarz A, Starkey NJ, Lubahn DB Tags: Curr Cancer Drug Targets Source Type: research