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Current Cancer Drug Targets

Jie Liu, Xiao Tan, Wennan Zhao, Jing Liu, Xiaoxue Xing, Guanwei Fan, Ping Zhang, Zhe Zhang, Yuxu Zhong, Dexin Kong
BACKGROUND: Metastasis is the main cause of lethality of prostate cancer. Inhibition of metastasis is expected to be a promising approach for prostate cancer therapy. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is known to play key roles in cell growth, migration, etc. Objective: Investigate the antimetastatic activities of pan-PI3K inhibitor ZSTK474 on prostate cancer DU145 cells. METHODS: 1. In vitro effect of ZSTK474 on the migration, invasion and adhesion of DU145 cells was determined with Transwell migration assay and wound healing assay, Tranwell invasion assay, and adhesion assay, respectively...
September 10, 2018: Current Cancer Drug Targets
Mousumi Tania, Jakaria Shawon, Kazi Saif, Rudolf Kiefer, Mahdi Safaei Khorram, Mohammad A Halim, Md Asaduzzaman Khan
Cordycepin is a small molecule from medicinal mushroom Cordyceps, which has been reported for anticancer properties. In this study, we investigated cordycepin effect on cervical cancer cells in vitro. Results indicate that treatment of cordycepin controlled SiHa and Hela cervical cancer cell growth, increased the rate of their apoptosis, and interfered with cell cycle, specifically elongated S-phase. By using qPCR, we investigated the expression of anti-apoptotic and pro-apoptotic proteins as well as cell cycle protein's expression in mRNA levels, and found there was a downregulation of cell cycle proteins CDK-2, CYCLIN-A2 and CYCLIN-E1 by cordycepin treatment but no significant change in pro-apoptotic or anti-apoptotic proteins...
September 4, 2018: Current Cancer Drug Targets
Merve Aksoz, Esra Albayrak, Galip Servet Aslan, Raife Dilek Turan, Lamia Yazgi Alyazici, Pinar Siyah, Emre Can Tusuz, Serli Canikyan, Dogacan Yucel, Neslihan Meric, Zafer Gulbas, Fikrettin Sahin, Fatih Kocabas
c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Targeting modulators of HSC quiescence and metabolism could lead to HSC cell cycle entry with concomitant expansion. Here we show that c-Myc inhibitor 10074-G5 treatment leads to 2-fold increase in murine LSKCD34low HSC compartment post 7 days. In addition, c-Myc inhibition increases CD34+ and CD133+ human HSC number. c-Myc inhibition leads to downregulation of glycolytic and cyclin-dependent kinase inhibitor (CDKI) gene expression ex vivo and in vivo...
September 4, 2018: Current Cancer Drug Targets
Md Zahidul I Pranjol, Nicholas J Gutowski, Michael Hannemann, Jacqueline L Whatmore
BACKGROUND: Metastasis still remains the major cause of therapeutic failure, poor prognosis and high mortality in epithelial ovarian cancer (EOC) patients. Previously, we showed that EOC cells secrete a range of factors with potential pro-angiogenic activity, in disease-relevant human microvascular omental endothelial cells (HOMECs), including the lysosomal protease cathepsin L (CathL). Thus, the aim of this study was to examine potential pro-proliferative and pro-migratory effects of CathL in HOMECs and the activated signalling pathways, and whether these proangiogenic responses are dependent on CathL-catalytic activity...
August 31, 2018: Current Cancer Drug Targets
Jie Wang, Haiyan Dong, Huayi Peng, Jian Liu, Ning Zheng, Xiaodong Xie, Lee Jia
BACKGROUND: one of the main reasons for the most of anticancer drugs fail in the late preclinical testing and early clinical trials is the differences in drug effects observed from animals and patients, and challenge has been to find a balance to reduce the inherent differences from species. OBJECTIVES: the animal toxicological studies of anticancer agents are aimed at predicting a safe starting dose and dosage regimen for human clinical trials. METHOD: relevant information and data were assimilated from manuscripts, congress publications, and online sources...
August 16, 2018: Current Cancer Drug Targets
Khalid Bashir Dar, Aashiq Hussain Bhat, Shajrul Amin, Syed Anjum, Bilal Ahmad Reshi, Mohammad Afzal Zargar, Akbar Masood, Showkat Ahmad Ganie
Protein-protein interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein we discuss the key protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors, adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting cancer...
August 2, 2018: Current Cancer Drug Targets
Linh N K Tran, Ganessan Kichenadasse, Pamela J Sykes
Prostate cancer (PCa) is the most frequent cancer in men. The evolution from local PCa to castration-resistant PCa, an end-stage of disease, is often associated with changes in genes such as p53, androgen receptor, PTEN, and ETS gene fusion products. Evidence is accumulating that repurposing of metformin (MET) and valproic acid (VPA) either when used alone, or in combination, with another therapy, could potentially play a role in slowing down PCa progression. This review provides an overview of the application of MET and VPA, both alone and in combination with other drugs for PCa treatment, correlates the responses to these drugs with common molecular changes in PCa, and then describes the potential for combined MET and VPA as a systemic therapy for prostate cancer, based on potential interacting mechanisms...
July 23, 2018: Current Cancer Drug Targets
Peng Liu, Hailin Tang, Jiali Wu, Xingsheng Qiu, Yanan Kong, Lijuan Zhang, Xinhua Xie, Xiangsheng Xiao
Long non-coding RNAs play crucial roles in various biological activities and diseases. The role of long intergenic non-coding RNA01638 (linc01638) in breast cancer, especially in HER2-positive breast cancer,remains largely unknown. In this study, linc01638 was found to be remarkably overexpressed in HER2-positive breast cancer cells and tissues. Suppression of linc01638 enhanced cell apoptosis, as well as inhibited the growth and invasiveness of HER2-positive breast cancer cells in vitro and tumor progression and metastasis in vivo...
July 9, 2018: Current Cancer Drug Targets
Zhou Jiang, Jiqing Ye, Jingyi Yang, Jian Wang, Lee Jia, Rodney Jy Hoc
Objective:To improve solubility and to reduce aggregation, ZnPcC4 was conjugated to a third-generation polyamidoamine dendrimer with amino end group (G3-PAMAM-NH2), which acts as a novel photodynamic therapy (PDT) drug carrier system. Method:The phthalocyanines were synthesized by construction reaction. The nanodrug was obtained from the conjugation of ZnPcC4 to G3-PAMAM-NH2, using EDC and NHS as coupling agents. The ZnPcC4@G3-PAMAM-NH2 conjugation was characterized by UV-Vis and MS. The 1O2 quantum yield of ZnPcC4@G3-PAMAM-NH2 in water was measured by the chemiluminescence method...
July 6, 2018: Current Cancer Drug Targets
Muhammad Furqan Akhtar, Ammara Saleem, Alamgeer Yuchi, Mohammad Saleem
The widespread emergence of cancer and development of resistance to chemotherapeutic agents is increasing the interest of scientists in the use of ethnomedicinal preparations and isolated phytochemicals in the treatment and prevention of disease. Medicinal plants are used in Pakistan for prehistoric times. The present review was designed to identify anticancer plants of ethnomedicinal significance and to summarize the anticancer activities carried out on these medicinal plants to establish the pharmacological and phytochemical basis for their use...
July 6, 2018: Current Cancer Drug Targets
Arkene Levy, Khalid Alhazzani, Priya Dondapati, Ali Alaseem, Khadijah Cheema, Keerthi Thallapureddy, Paramajot Kaur, Saad Alobid, Appu Rathinavelu
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase, which is an essential player in regulating cell migration, invasion, adhesion, proliferation, and survival. Its overexpression and activation have been identified in sixty-eight percent of epithelial ovarian cancer patients and this is significantly associated with higher tumor stage, metastasis, and shorter overall survival of these patients. Most recently, a new role has emerged for FAK in promoting resistance to taxane and platinum based therapy in ovarian and other cancers...
July 6, 2018: Current Cancer Drug Targets
Karthikeyan Subbarayan, Barbara Seliger
BACKGROUND: The small leucine-rich proteoglycans (SLRPs) biglycan (BGN) and decorin (DCN) linked with sulfated glycosaminoglycan (GAG) chains exhibit oncogenic or tumor suppressive potentials depending on the cellular context and association with GAGs. OBJECTIVE: We hypothesized that structural alterations and expression levels of BGN, DCN and their associated chondroitin sulfate (CS) polymerizing enzymes, dermatan sulfate (DS) epimerases and various sulfatases might be correlated with the tumor (sub)type and patients' survival...
July 6, 2018: Current Cancer Drug Targets
Junsong Chen, Na Niu, Jing Zhang, Lisha Qi, Weiwei Shen, Krishna Vanaja Donkena, Zhenqing Feng, Jinsong Liu
Polyploidy is associated with increased cell size and commonly found in a subset of adult organs and blastomere stage of human embryo. The polyploidy is formed through endoreplication or cell fusion to support specific need of development including earliest embryogenesis. Recent data demonstrated that polyploid giant cancer cells (PGCCs) may have acquired an activated early embryonic-like program in response to oncogenic and therapeutic stress to generate reprogrammed cancer cells for drug resistance and metastasis...
July 3, 2018: Current Cancer Drug Targets
Yanping Cao, Zhihao Wei, Mengmeng Li, Haiyan Wang, Li Yin, Dongxiao Chen, Yanfei Wang, Yongchao Chen, Qi Yuan, Xiaohui Pu, Lanlan Zong, Shaofeng Duan
BACKGROUND: Improving poorly soluble drugs into druggability was a major problem faced by pharmaceutists. Nanosuspension can improve the druggability of insoluble drugs by improving the solubility, chemical stability and reducing the use of additives, which provided a new approach for the development and application of the insoluble drugs formulation. Paclitaxel (PTX) is a well-known BCS class IV drug with poor solubility and permeability. Also, many studies have proved that paclitaxel is a substrate of the membrane-bound drug efflux pump P-glycoprotein (P-gp), therefore it often shows limited efficacy against the resistant tumors and oral absorption or uptake...
June 29, 2018: Current Cancer Drug Targets
Xiaodong Xie, Yingying Zhang, Fengqiao Li, Tingting Lv, Ziying Li, Haijun Chen, Lee Jia, Yu Gao
BACKGROUND: Effective cancer therapy is still a great challenge for modern medical research due to the complex underlying mechanisms of tumorigenesis and tumor metastasis, and the limitations commonly associated with currently used cancer therapeutic options. Nanotechnology has been implemented in cancer therapeutics with immense potential for improving cancer treatment. OBJECTIVES: Through information about the recent advances regarding cancer hallmarks, we could comprehensively understand the pharmacological effects and explore the mechanisms of the interaction between the nanomaterials, which could provide opportunities to develop mechanism-based nanomedicine to treat human cancers through...
June 28, 2018: Current Cancer Drug Targets
Hamidreza Maroof, Soussan Irani, Armin Ariana, Jelena Vider, Vinod Gopalan, Alfred King-Yin Lam
BACKGROUND: The clinical pathological features as well as the cellular mechanisms of miR-195 have not been investigated in thyroid carcinoma. OBJECTIVE: The aim of this study is to identify the interactions of vascular endothelial growth factor (VEGF), p53 and miR-195 in thyroid carcinoma. The clinical and pathological features of miR-195 were also investigated. METHOD: The expression levels of miR-195 were identified in 123 primary thyroid carcinomas, 40 lymph nodes with metastatic papillary thyroid carcinomas and seven non-neoplastic thyroid tissues (controls) as well as two thyroid carcinoma cell lines, B-CPAP (from metastasizing human papillary thyroid carcinoma) and MB-1 (from anaplastic thyroid carcinoma), by the real-time polymerase chain reaction...
June 28, 2018: Current Cancer Drug Targets
Ishita Tandon, Nilesh Kumar Sharma
Tumor heterogeneity within various cancer types including breast carcinoma is pivotal in the manifestations of tumor hallmarks. Tumor heterogeneity is seen as a common landscape where intra-tumoral components including cellular and non-cellular factors create interface with outside environment that lead to the unique identity of a specific cancer type. Among various contributors to tumor heterogeneity, cellular heterogeneity immensely plays a role in drug resistance and relapse of cancer. Within cellular heterogeneity of tumor, tumor-associated macrophages (TAMs) are pro-tumor type of immune cells that promote growth, metastasis and drug resistance in breast carcinoma and other cancer types...
June 27, 2018: Current Cancer Drug Targets
Guillaume Poiroux, Annick Barre, Pierre Rouge, Herve Benoist
The use of photodynamic therapy in cancer still remains limited, partly because of the lack of photosensitizer (PS) specificity for the cancerous tissues. Various molecular tools are available to increase PS efficiency by targeting the cancer cell molecular alterations. The most strategies use the protein-protein interactions, e.g. monoclonal antibodies directed toward tumor antigens, such as HER2 or EGFR. An alternative could be the targeting of the tumor glycosylation aberrations, e.g. T/Tn antigens that are truncated O-glycans over-expressed in numerous tumors...
June 27, 2018: Current Cancer Drug Targets
Peng Liu, Yanfang Wu, Ziwen Lu, Dongsheng Shang, Zhicong Zhao, Yanting Shen, Yafei Zhang, Feifei Zhu, Hanqing Liu, Zhigang Tu
BACKGROUND: Recently, the chemotherapeutic drug-induced cellular senescence is considered per se a promising anti-cancer approach. This drug-induced senescence, which shows both similar, and different hallmarks from replicative senescence and oncogene-induced senescence, was regarded as a key determinant of tumor response to chemotherapy in vitro and in vivo. To date, plenty of effective chemotherapeutic drugs that evoke senescence in cancer cells have been reported. The targets of these drugs differ substantially from each other, as well as from DNA damage response, telomerase activity inhibition through senescence-related CDK, p53 and Rb signaling pathways...
May 29, 2018: Current Cancer Drug Targets
Xiang Zhang, Wei Zhang, Xing-Gang Mao, Wei-Dong Cao, Hai-Ning Zhen, Shi-Jie Hu
Malignant high grade glioma (HGG) is the most common and extremely fatal type of primary intracranial tumor. These tumors recurred within 2 to 3 cm of the primary region of tumor resection in the majority of cases. Furthermore, the blood-brain barrier significantly limited the access of many systemically administered chemotherapeutics to the tumor, pointing towards a stringent need for new therapeutic patterns. Therefore, targeting therapy using local drug delivery for HGG becomes a priority for the development of novel therapeutic strategies...
May 29, 2018: Current Cancer Drug Targets
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