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Current Cancer Drug Targets

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https://www.readbyqxmd.com/read/28530531/the-complexity-of-dek-signaling-in-cancer-progression
#1
Yong Teng, Liwei Lang, Catherine E Jauregui
The DNA binding protein and chromatin structural regulator DEK regulates many cellular processes. These include proliferation, differentiation, apoptosis, senescence, DNA repairing and the maintenance of stem cell phenotype. DEK is increasingly recognized as a crucial player in many steps of cancer initiation and progression, and is precisely regulated by abundant promoting and inhibiting factors directly or indirectly. DEK may serve as an architectural modulating protein to regulate the expression and function of multiple human genes in cancer cells...
May 21, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28464762/cancer-targeted-oncolytic-adenoviruses-for-modulation-of-the-immune-system
#2
Vincenzo Cerullo, Cristian Capasso, Markus Vähä-Koskela, Otto Hemminki, Akseli Hemminki
Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen-presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit...
May 2, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28460620/cx-4945-a-selective-inhibitor-of-casein-kinase-2-synergizes-with-b-cell-receptor-signaling-inhibitors-in-inducing-diffuse-large-b-cell-lymphoma-cell-death
#3
Elisa Mandato, Sara Canovas Nunes, Fortunato Zaffino, Alessandro Casellato, Paolo Macaccaro, Laura Quotti Tubi, Andrea Visentin, Livio Trentin, Gianpietro Semenzato, Francesco Piazza
BACKGROUND: Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and promotes a "non-oncogene addiction" phenotype. Whether this kinase regulates BCR signaling thus being a suitable pharmacological target in DLBCL is unknown. OBJECTIVE: To establish if CK2 controls DLBCL cell survival and the BCR signaling; to check if the combination of CK2 inhibitor CX-4945 and BCR blockers Ibrutinib and Fostamatinib is more effectively cytotoxic for DLBCL cells than the single agents; to survey the changes in signaling molecules downstream BCR upon CK2 inhibition...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28460619/targeting-steap1-protein-in-human-cancer-current-trends-and-future-challenges
#4
Jorge Barroca-Ferreira, João Pedro Pais, Margarida Maria Santos, Ana Margarida Gonçalves, Inês Margarida Gomes, Inês Margarida Sousa, Sandra Moreira Rocha, Luís António Passarinha, Cláudio Maia
Cancer is a global health issue that impairs the life quality of patients and origins thousands of deaths annually worldwide. Six-transmembrane epithelial antigen of the prostate (STEAP1) was identified to be overexpressed in several types of cancers, namely in prostate cancer (PCa). Considering its secondary structure, associated with its location in the cell membrane, has been suggested a role in intercellular communication between tumour cells. Taking into account its high specificity and overexpression in human cancers, STEAP1 is nowadays a promising candidate to be imposed as a therapeutic target...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28460618/specific-targeting-of-her2-positive-head-and-neck-squamous-cell-carcinoma-line-hn5-by-idarubicin-zher2-affibody-conjugate
#5
Marzieh Ghanemi, Aminollah Pourshohod, Mohammad Ali Ghaffari, Alireza Kheirollah, Mansour Amin, Majid Zeinali, Mostafa Jamalan
Expression of human epidermal growth factor receptor type 2 (HER2) in head and neck squamous cell carcinoma (HNSCC) cell line HN5 can be employed with great opportunities of success for specific targeting of anti-cancer chemotherapeutic agents. In the current study, HER2-specific affibody molecule, ZHER2:342 (an engineered protein with great affinity for HER2 receptors) was selected for conjugation to idarubicin (an anti-neoplastic antibiotic). ZHER2:342 affibody gene with one added cysteine code at the its 5' end was synthesized de novo and then inserted into pET302 plasmid and transferred to E...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28460617/impact-of-il-12-in-cancer
#6
Xinjie Lu
BACKGROUND: Interleukin 12 (IL-12) is a pleiotropic cytokine that plays an essential role in Th1-type immune response against cancer, a condition where cells in a particular part of the body grow and reproduce uncontrollably. METHODS: In this review, we describe the structural features of IL-12 family and their roles involved in cancer. RESULTS: IL-12 has been demonstrated to regulate both innate (natural killer cells) and adaptive (cytotoxic T lymphocytes) immunities in cancer therapy...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28460616/epithelial-to-mesenchymal-transition-a-mediator-of-sorafenib-resistance-in-advanced-hepatocellular-carcinoma
#7
Nabiel Mir, Aparna Jayachandran, Bijay Dhungel, Ritu Shrestha, Jason C Steel
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide and its incidence is steadily rising. Currently, sorafenib remains the only approved standard treatment for patients with advanced HCC, as it has proven to increase survival in these patients. However, clinical and preclinical observations indicate that sorafenib treatment may have limited efficacy due to tumor progression from the rapid development of acquired resistance. Elucidation of the underlying mechanisms of evasive resistance to sorafenib is a major challenge in HCC research...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359250/insight-into-discovery-of-next-generation-reversible-tmlr-inhibitors-targeting-egfr-activating-and-drug-resistant-t790m-mutants
#8
Subhash Mohan Agarwal, Divyani Pal, Mansi Gupta, Ravi Saini
Cancer is one of the most challenging diseases among the various causes of deaths worldwide. Among cancer, lung cancer rules as the leading cause of cancer-related deaths annually.The majority of the lung cancers identified are non-small cell lung cancer (NSCLC). Clinically, the Epidermal Growth Factor Receptor (EGFR) is a therapeutically accepted target for NSCLC. Many therapeutic leads that target this transmembrane receptor protein were tested for anti-EGFR activity that led to the discovery of gefitinib and erlotinib...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359249/autophagy-inhibition-in-childhood-nephroblastoma-and-the-therapeutic-significance
#9
Lin-Jie Li, Yi-Long Wang, Lin-Qing Yuan, Wei-Zhong Gu, Kun Zhu, Min Yang, Duo Zhou, Yao Lv, Min-Ju Li, Zheng-Yan Zhao, Jin-Hu Wang, Xi Chen
Autophagy is a physiological pathway characterized by lysosome-dependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy hampers the maintenance of cellular homeostasis and contributes to tumorigenesis. However, during anticancer therapy, autophagy activation contributes to development of resistance. Thus autophagy has been recognized as an important pathway and a therapeutic target in cancer. Nephroblastoma (Wilm's tumor) is a common childhood malignancy, the prognosis of the metastatic and relapsed cases remains poor...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359248/immunomodulatory-activity-of-micrornas-potential-implications-for-multiple-myeloma-treatment
#10
Cirino Botta, Maria Cucè, Daniele Caracciolo, Lucia Fiorillo, Pierosandro Tagliaferri, Pierfrancesco Tassone
Multiple myeloma (MM) is an incurable plasma cell neoplasm accounting for about 10% of all hematologic malignancies. Recently, emerging evidence is disclosing the complexity of bone marrow interactions between MM cells and infiltrating immune cells, which have been reported to promote proliferation, survival and drug resistance of tumor cells. MicroRNAs (miRNAs) are small non-coding RNA molecules with regulatory functions in the cell, whose expression has predictive and prognostic value in different malignancies...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359247/method-to-assess-interactivity-of-drugs-with-nonparallel-concentration-effect-relationships
#11
Liang Zhao, Jessie L-S Au, M Guillaume Wientjes
BACKGROUND: Commonly used methods for analyzing interactivity between drugs (e.g., synergy, antagonism) such as isobologram, combination index, and curve shift are based on the Loewe Additivity principle of dose equivalence and the inherent assumption of similar concentration-effect (C-E) including parallel curves and equal maximum effects (Emax), and therefore are not suitable for drugs with dissimilar C-E. This study describes a new method that is without this limitation and has the additional advantage of enabling statistical analysis...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359246/in-silico-in-vitro-identification-of-structure-activity-relationship-pattern-of-serpentine-gallic-acid-targeting-pi3k%C3%AE-as-potential-anticancer-target
#12
Pooja Sharma, Aparna Shukla, Komal Kalani, Vijaya Dubey, Suaib Luqman, S K Srivastava, Feroz Khan
Natural products showed anticancer activity and often induce apoptosis or autophagy in cancer cells through the PI3K/Akt/mTOR signaling pathways. The potential of natural products as PI3Ks inhibitors has been reported, which suggest PI3Ks a promising anticancer target. Phosphoinositide 3-kinase (PI3K) is a family of related intracellular signal transducer enzymes or lipid kinases that regulate different cellular processes involved in cancer. In the studied work, anticancer potential of two active plant secondary metabolites, namely gallic acid and serpentine was evaluated against PI3Ks, especially gamma isoform and compared with the wortmannin, a steroid metabolite of the fungi and a non-specific covalent known inhibitor of PI3Ks, based on in-silico QSAR, molecular docking, eADMET and in-vitro activity...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359245/the-%C3%AE-2-adrenergic-agonist-salbutamol-inhibits-migration-invasion-and-metastasis-of-the-human-breast-cancer-mda-mb-231-cell-line
#13
Ezequiel Mariano Rivero, Cecilia Pérez Piñero, Lucía Gargiulo, Frank Entschladen, Kurt Zänker, Ariana Bruzzone, Isabel Alicia Lüthy
BACKGROUND: Breast cancer is the most diagnosed and the major cause of cancer death in women worldwide. Metastasis is the main cause of these deaths. The metastatic cascade involves multiple steps and it has been described that adrenergic receptors can modulate this process at multiple levels. However, β-adrenergic action in breast cancer is controversial. We have previously shown that β-adrenergic agonists inhibit cell proliferation and tumor growth of numerous breast cancer models...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359244/potential-therapeutic-targets-in-energy-metabolism-pathways-of-breast-cancer
#14
Rowshan Ara Islam, Sazzad Hossain, Ezharul Hoque Chowdhury
Mutations in proto-oncogenes and tumor suppressor genes make cancer cells proliferate indefinitely. As they possess almost all mechanisms for cell proliferation and survival like healthy cells, it is difficult to specifically target cancer cells in the body. Current treatments in most of the cases are harmful to healthy cells as well. Thus, it would be of great prudence to target specific characters of cancer cells. Since cancer cells avidly use glucose and glutamine to survive and proliferate by upregulating the relevant enzymes and their specific isoforms having important regulatory roles, it has been of great interest recently to target the energy-related metabolic pathways as part of the therapeutic interventions...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359243/redox-biotransformation-and-delivery-of-anthracycline-anticancer-antibiotics-how-interpretable-structure-activity-relationships-of-lethality-using-electrophilicity-and-the-london-formula-for-dispersion-interaction-work
#15
Siu-Kwong Pang
Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359242/small-molecule-inhibitors-of-epigenetic-mutations-as-compelling-drug-targets-for-myelodysplastic-syndromes
#16
Bani Bandana Ganguly
BACKGROUND: Involvement of mutations in epigenetic mechanism in development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359241/obesity-and-cancer-biological-links-and-treatment-implications
#17
Alessandro Ottaiano, Chiara De Divitiis, Monica Capozzi, Antonio Avallone, Carmen Pisano, Sandro Pignata, Salvatore Tafuto
Obesity is an epidemic disease and correlates with cardiovascular diseases increasing the overall mortality. However, it has been recently demonstrated that cancer is an unexpected consequence of obesity. In most of the studies it is evaluated with body mass index (BMI): high BMI increases cancer risk and reduces survival of many solid tumors. The main biologic and clinic topics regarding obese cancer patients are here presented and discussed. Hyperinsulinemia and Insulin-like Growth Factors (IGFs) are among the most important links between cancer and obesity...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359240/elaborating-the-role-of-natural-products-on-the-regulation-of-autophagy-and-their-potentials-in-breast-cancer-therapy
#18
Xunian Zhou, Grace Gar-Lee Yue, Stephen Kwok-Wing Tsui, Jianxin Pu, Kwok-Pui Fung, Clara Bik-San Lau
Autophagy is an intracellular lysosomal/vacuolar degradation system, which the inner cytoplasmic cell membrane is degraded by the lysosomal hydrolases, followed by the resulting products released back into the cytosol. It is involved in many physiological processes which are crucial for cell growth and survival. However, disturbance in the autophagic process is often associated with a variety of human diseases, such as cancer. Breast cancer is one of the most malignant tumors characterized by the imbalanced cell proliferation, apoptosis as well as disordered autophagy regulation...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359239/oncolytic-virotherapy-and-gene-therapy-strategies-for-hepatobiliary-cancers
#19
Takeshi Yamada, Yukako Hamano, Naoyuki Hasegawa, Kazunari K Yokoyama, Ichinosuke Hyodo, Masato Abei
Advanced liver cancers and biliary cancers represent diseases with dismal prognosis because of frequent local invasion and metastasis. Effective therapeutic agents for these cancers have not been established. Oncolytic viruses (OVs) constitute a novel class of promising, selective anticancer agents and recent studies have elucidated their unique features. Moreover, clinical trials are demonstrating promising results. Numerous OVs are being tested in preclinical models of hepatocellular carcinoma (HCC). The lead agent Pexa-Vec (pexastimogene devacirepvec, JX-594) , a recombinant Wyeth strain vaccinia virus, has demonstrated preliminary evidence of safety and efficacy for HCC in clinical trials...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359238/hr-her2-advanced-breast-cancer-and-cdk4-6-inhibitors-mode-of-action-clinical-activity-and-safety-profiles
#20
Sarah L Sammons, Donna L Topping, Kimberly L Blackwell
Cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapies have shown great promise in improving clinical outcomes for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Addition of a CDK4/6 inhibitor to endocrine therapy increases efficacy and delays disease progression. Successful use of CDK4/6 inhibitor-based therapies in the clinic requires insight into the unique side-effect profiles of this class of agents and effective patient monitoring...
March 30, 2017: Current Cancer Drug Targets
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