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Current Cancer Drug Targets

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https://www.readbyqxmd.com/read/28359250/insight-into-discovery-of-next-generation-reversible-tmlr-inhibitors-targeting-egfr-activating-and-drug-resistant-t790m-mutants
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28359237/influence-of-aldo-keto-reductase-1c3-in-prostate-cancer-a-mini-review
#14
Nishi Karunasingh, Jonathan Masters, Jack U Flanagan, Lynnette R Ferguson
Aldo-keto reductase 1C3 (AKR1C3) is an important oxidoreductase with multiple substrates, that is involved in producing extra-testicular androgens. Its activity is influenced by environmental exposures, as well as by genetic variants. These genetic variants could therefore produce variable testosterone levels and subsequent androgen receptor (AR) activation. This could lead to differential downstream production of the prostate-specific antigen (PSA). As PSA level is used for clinical evaluation of the prostate, these variations could impact prostate cancer (PC) diagnosis, as well as PC management outcomes...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359236/effects-of-pha-665752-and-cetuximab-combination-treatment-on-in-vitro-and-murine-xenograft-growth-of-human-colorectal-cancer-cells-with-kras-or-braf-mutations
#15
Yi-Tao Jia, Dong-Hai Yang, Zhaolong Zhao, Xiao-Hui Bi, Wei-Hua Han, Bo Feng, Jie Zhi, Bin Gu, Zhihui Duan, Jian-Hua Wu, Ying-Chao Ju, Ming-Xia Wang, Zhong-Xin Li
BACKGROUND: It remains unknown whether blockade of c-Met signaling and epidermal growth factor receptor signaling is effective in suppressing the growth of human colorectal cancer (CRC) cells. In this study, we investigated the effects of the c-Met inhibitor PHA-665752 alone and in combination with cetuximab on the growth of human CRC cells in vitro and in mouse xenografts. METHODS: Human CRC cell lines (Caco2, HCT-116, and HT-29) and mice bearing HCT-116 xenografts were treated with cetuximab in the absence or presence of PHA-665752...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28302032/anti-tumorigenic-effects-of-resveratrol-in-lung-cancer-cells-through-modulation-of-c-flip
#16
Clayton Wright, Anand Krishnan V Iyer, Juan S Yakisich, Neelam Azad
Resveratrol has been shown to have antioxidant and anti-proliferative properties in multiple cancer types. Here we demonstrate that H460 lung cancer cells are more susceptible to resveratrol treatment in comparison to human bronchial epithelial Beas-2B cells. Resveratrol decreases cell viability and proliferation, and induces significant apoptosis in H460 cells. The apoptosis observed was accompanied by an increase in hydrogen peroxide (H2O2) production, Bid, PARP and caspase 8 activation, and downregulation of pEGFR, pAkt, c-FLIP and NFkB protein expression...
March 15, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28302031/hif1a-is-overexpressed-in-medulloblastoma-and-its-inhibition-reduces-proliferation-and-increases-epas1-and-atg16l1-methylation
#17
Gustavo Alencastro Veiga Cruzeiro, Maristella Bergamo Dos Reis, Vanessa Silva Silveira, Régia Caroline Peixoto Lira, Carlos Gilberto Carlotti, Luciano Neder, Ricardo Santos Oliveira, José Andres Yunes, Silvia Regina Brandalise, Simone Aguiar, Agda Karina Eterovic, Luiz Gonzaga Tone, Carlos Alberto Scrideli, Elvis Terci Valera
BACKGROUND: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxia-related genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions...
March 15, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28228086/clinical-trials-with-oncolytic-measles-virus-current-status-and-future-prospects
#18
Pavlos Msaouel, Mateusz Opyrchal, Angela Dispenzieri, Kah Whye Peng, Mark J Federspiel, Stephen J Russell, Evanthia Galanis
Attenuated Edmonston lineage measles virus (MV-Edm) vaccine strains can preferentially infect and lyse a wide variety of cancer cells. Oncolytic MV-Edm derivatives genetically engineered to expressed the human carcinoembryonic antigen (MV-CEA virus) or the human sodium iodide symporter (MV-NIS virus) and are currently being tested in clinical trials against ovarian cancer, glioblastoma multiforme, multiple myeloma, mesothelioma, head and neck cancer, breast cancer and malignant peripheral nerve sheath tumors...
February 22, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28228085/emergence-of-ad-mediated-combination-therapy-against-cancer-what-to-expect
#19
JinWoo Hong, Chae-Ok Yun
Novel treatment modalities are rapidly advancing toward clinical use as many malignant cancers still remain incurable. Adenovirus (Ad) in particular has been extensively researched as a promising alternative to conventional cancer therapy in the past decades. Although Ad has demonstrated promising therapeutic outcome and cancer-specificity in preclinical models, its therapeutic efficacy in clinical trials is still insufficient due to several drawbacks such as rapid clearance of viral particles by host immune response, induction of acute inflammatory response, and hepatotoxicity...
February 22, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28228084/the-development-of-oncoltyic-adenovirus-therapy-in-the-past-and-future-for-the-case-of-pancreatic-cancer
#20
Mizuho Sato-Dahlman, Masato Yamamoto
Pancreatic cancer is an aggressive malignant disease and the efficacy of current treatments for unresectable diseases is quite limited despite recent advances. Gene therapy /virotherapy strategies may provide new options for treatment of various cancers including pancreatic cancer. Oncolytic adenovirus shows an antitumoral effect via its intratumoral amplification and strong cytocidal effect in a variety of cancers and it has been employed for the development of potent oncolytic virotherapy agents for pancreatic cancer...
February 22, 2017: Current Cancer Drug Targets
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