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drug resistance cancer

Bilal Houshaymi, Nadine Nasreddine, Mamdouh Kedees, Zeina Soayfane
The bioavailability of ivermectin is modulated by lipid-based formulations and membrane efflux transporters such as Breast Cancer Resistance Protein and P-glycoprotein (BCRP and P-gp). We have investigated the effect of oleic acid on the uptake of ivermectin in vitro using Caco-2 cells and in vivo in the intestines of wild-type mice. Complex micelles (M) with oleic acid induced a significant increase (e. g. for M3 was 7-fold, p≤0.001) in the uptake of the drug in a time-dependent manner with no involvement of cholesterol in the mechanism...
August 13, 2018: Drug Research
M Orditura, C M Della Corte, A Diana, V Ciaramella, E Franzese, V Famiglietti, I Panarese, R Franco, A Grimaldi, A Lombardi, M Caraglia, A Santoriello, E Procaccini, E Lieto, E Maiello, F De Vita, F Ciardiello, F Morgillo
Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in breast cancer (BC) patients. We have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT-inibitors in combination with anti-microtubule drugs in human BC cell lines, through a complete cytoskeleton disorganization. In this work, we generated ex-vivo three-dimensional (3D) cultures from human BC as a model to test drug efficacy and to identify new molecular biomarkers for selection of BC patients suitable for anti-PI3K/AKT-inibitors treatment...
August 4, 2018: Breast: Official Journal of the European Society of Mastology
Yibao Ma, Sarah M Temkin, Adam M Hawkridge, Chunqing Guo, Wei Wang, Xiang-Yang Wang, Xianjun Fang
Cancer cells undergo metabolic reprogramming such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid cycle enzymes, and upregulation of de novo lipid synthesis and glutaminolysis. These alterations are pivotal to the development and maintenance of the malignant phenotype of cancer cells in unfavorable tumor microenvironment or metastatic sites. Although mitochondrial fatty acid β-oxidation (FAO) is a primary bioenergetic source, it has not been generally recognized as part of the metabolic landscape of cancer...
August 10, 2018: Cancer Letters
Mohammad Askandar Iqbal, Shweta Arora, Gopinath Prakasam, George A Calin, Mansoor Ali Syed
Lung cancer is the cardinal cause of cancer-related deaths with restricted recourse of therapy throughout the world. Clinical success of therapies is not very promising due to - late diagnosis, limited therapeutic tools, relapse and the development of drug resistance. Recently, small ∼20-24 nucleotides molecules called microRNAs (miRNAs) have come into the limelight as they play outstanding role in the process of tumorigenesis by regulating cell cycle, metastasis, angiogenesis, metabolism and apoptosis. miRNAs essentially regulate gene expression via post-transcriptional regulation of mRNA...
August 10, 2018: Molecular Aspects of Medicine
Afu Fu, Yu Ming Peh, Weida Ngan, Na Wei, Kathy Qian Luo
Treating systemic metastases at the micrometastatic stage is a potential strategy to inhibit cancer metastasis. This study aims to establish an apoptosis sensor-based platform for rapid, effective, and non-invasive identification of drugs that can inhibit the proliferation of micrometastatic cancer cells. We stably transfected the plasmid DNA encoding the fluorescence resonance energy transfer (FRET)-based caspase-3 sensor into highly metastatic melanoma B16F10 cells. The resulting B16F10-C3 cells were applied for screening of anti-proliferative and pro-apoptotic drugs in two-dimensional (2D) monolayer, three-dimensional (3D) spheroids, and zebrafish xenotransplantation tumors...
August 13, 2018: Biotechnology and Bioengineering
Rafael G Dos Santos, José Carlos Bouso, Miguel Ángel Alcázar-Córcoles, Jaime E C Hallak
Mood, anxiety, and substance use disorders are among the most prevalent psychiatric disorders in the population. Although several pharmacological treatments are available, they are not effective for a significant proportion of patients and are associated with several adverse reactions. Therefore, new treatments should be explored. Recent with serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin and lysergic acid diethylamide (LSD) suggest that these drugs have anxiolytic, antidepressive, and antiaddictive effects...
August 13, 2018: Expert Review of Clinical Pharmacology
Dana E Rathkopf, Howard I Scher
Five new agents have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer, including two targeting androgen receptor signaling (abiraterone acetate plus prednisone; enzalutamide). Recognition that these tumors remain driven by androgen receptor signaling has prompted clinical evaluation of these agents at earlier states in the prostate cancer disease continuum, along with the continued development of new agents targeting this pathway. Areas covered: This article focuses on apalutamide, a next-generation nonsteroidal antiandrogen, with current literature queried in PubMed/Medline...
September 2018: Expert Review of Anticancer Therapy
Giovanni Ribaudo, Enrico Zanforlin, Giuseppe Zagotto
The introduction of tyrosine kinase inhibitors (TKIs) in the clinical management of oncological patients spread the light on the use of selective, rationally designed small molecules for the treatment of cancer. First-generation TKIs bared high response against these malignancies, although the unavoidable shadow of resistance limits their long-term efficacy. Non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, and it is the first cause of cancer deaths worldwide for men and women. Traditional chemotherapy is marginally effective against this form, and erlotinib and gefitinib were introduced as first-line treatments based on the observation that the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK), is mutated in several cases and, thus, represents a druggable target...
August 12, 2018: Archiv der Pharmazie
Chiara Oltolini, Marco Ripa, Andrea Andolina, Elena Brioschi, Marta Cilla, Giovanna Petrella, Vanesa Gregorc, Barbara Castiglioni, Chiara Tassan Din, Paolo Scarpellini
The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile. Regarding infectious complications, it has emerged that these compounds do not intrinsically increase susceptibility to opportunistic infections, which mainly correlate with the co-administration of systemic immunosuppressive therapy (high-dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune-related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well-known complications of these targeted drugs...
August 13, 2018: Mycopathologia
Ying Zhang, Bin Xu, Xi-Ping Zhang
Breast cancer is one of the most common malignancies for women, which accounts for 30% of all female malignancies. The formation of breast cancer stem cells (BCSCs) is attributed to the acquisition of stemness of tumor cells. With self-renewal potential, these stem cells are insensitive to either radiotherapy or chemotherapy but are significant in regulating tumor behaviors and drug resistance. MicroRNA (miRNA) is a kind of noncoding small RNA for negatively regulating gene expressions. Research findings suggest that many miRNAs specifically regulate the expression of target genes and signal pathways of BCSCs...
2018: OncoTargets and Therapy
Radoslav Chekerov, Felix Hilpert, Sven Mahner, Ahmed El-Balat, Philipp Harter, Nikolaus De Gregorio, Claudius Fridrich, Susanne Markmann, Jochem Potenberg, Ralf Lorenz, Guelten Oskay-Oezcelik, Marcus Schmidt, Petra Krabisch, Hans-Joachim Lueck, Rolf Richter, Elena Ioana Braicu, Andreas du Bois, Jalid Sehouli
BACKGROUND: Antiangiogenic therapy has known activity in ovarian cancer. The investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase inhibitor sorafenib combined with topotecan and continued as maintenance therapy for platinum-resistant or platinum-refractory ovarian cancer. METHODS: We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20 sites in Germany. Patients (≥18 years) with platinum-resistant ovarian cancer previously treated with two or fewer chemotherapy lines for recurrent disease were stratified (first vs later relapse) in block sizes of four and randomly assigned (1:1) using a web-generated response system to topotecan (1·25 mg/m2 on days 1-5) plus either oral sorafenib 400 mg or placebo twice daily on days 6-15, repeated every 21 days for six cycles, followed by daily maintenance sorafenib or placebo for up to 1 year in patients without progression...
August 9, 2018: Lancet Oncology
Ning Xu, Shaomu Chen, Yufeng Liu, Wei Li, Zeyi Liu, Xiaojie Bian, Chunhua Ling, Min Jiang
BACKGROUND/AIMS: Circular RNAs (circRNAs) act as microRNA (miRNA) sponges that regulate gene expression and are involved in physiological and pathological processes. In this study, we evaluated the roles of circRNAs in the chemoresistance of non-small cell lung cancer (NSCLC) to taxol. METHODS: High-throughput circRNA microarrays were employed to investigate the circRNA profiles of parental A549 and taxol-resistant A549/Taxol cells. We predicted the miRNA targets of differentially expressed circRNAs via miRNA prediction software and then constructed a circRNA/miRNA network using Cytoscape...
August 10, 2018: Cellular Physiology and Biochemistry
Yuanxin Tian, Yunci Ma, Shaoyu Wu, Tingting Zhang, Zhonghuang Li, Guangfa Wang, Jiajie Zhang
Receptor Tyrosine Kinase inhibitors are the most popular anti-cancer drug types. But the resistance is the major challenge. Our study on the network with 1334 proteins and their 2623 interactions which retrieved from 52 RTKs indicated that most RTKs proteins were the key controllers of the protein-protein network. Direct or indirect interactions with RTKs (shortest path of 2) were often associated with resistance to RTKs inhibitors in the literature. The results based on the KEGG pathway analysis demonstrated the Rap1 signal pathway would also contribute to the resistance of RTKs inhibitor as well as the known Ras pathway and PI3K/Akt pathway...
August 3, 2018: Computational Biology and Chemistry
Gianpiero Lazzari, Valerie Nicolas, Michiya Matsusaki, Mitsuru Akashi, Patrick Couvreur, Simona Mura
The preclinical drug screening of pancreatic cancer treatments suffers from the absence of appropriate models capable to reproduce in vitro the heterogeneous tumor microenvironment and its stiff desmoplasia. Driven by this pressing need, we describe in this paper the conception and the characterization of a novel 3D tumor model, consisting of a triple co-culture of pancreatic cancer cells (PANC-1), fibroblasts (MRC-5) and endothelial cells (HUVEC), which assembled to form a hetero-type multicellular tumor spheroid (MCTS)...
August 9, 2018: Acta Biomaterialia
Danh Truong, Roberto Fiorelli, Eric S Barrientos, Ernesto Luna Melendez, Nader Sanai, Shwetal Mehta, Mehdi Nikkhah
Glioblastoma (GBM) is one of the deadliest forms of cancer. Despite many treatment options, prognosis of GBM remains dismal with a 5-year survival rate of 4.7%. Even then, tumors often recur after treatment. Tumor recurrence is hypothesized to be driven by glioma stem cell (GSC) populations which are highly tumorigenic, invasive, and resistant to several forms of therapy. GSCs are often concentrated around the tumor vasculature, referred to as the vascular niche, which are known to provide microenvironmental cues to maintain GSC stemness, promote invasion, and resistance to therapies...
July 30, 2018: Biomaterials
Francesca Maria Rizzo, Tim Meyer
Effective management of neuroendocrine tumors depends on early diagnosis, personalized risk stratification, and monitoring response to therapy. During cancer progression, tumors shed circulating tumor cells, circulating tumor DNA, and microRNAs into the bloodstream. Analysis of these biomarkers offers the prospect of a liquid biopsy to predict/monitor therapeutic responses, assess drug resistance, and quantify residual disease. Compared with single-site biopsies, these entities have the potential to inform intratumor heterogeneity and tumor evolution in a reproducible and less invasive way...
September 2018: Endocrinology and Metabolism Clinics of North America
Hemanth Naick Banavath, Srinivasa Rao Allam, Stella Sravanthi Valathati, Alok Sharan, Baskaran Rajasekaran
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder occurs in the pluripotent hematopoietic stem cell. Currently, first-generation tyrosine kinase inhibitor (TKI) imatinib is the mainstay for the treatment of CML. Second generation TKI's like ponatinib, dasatinib, nilotinib, and bafetinib were treated against resistant CML. However, several CML patients develop resistance towards all existing inhibitors. Curcumin (Curcuma longa) a plant-derived natural compound is an effective bioactive component against various cancers including CML...
July 31, 2018: Journal of Photochemistry and Photobiology. B, Biology
Katerina Stanková, Joel S Brown, William S Dalton, Robert A Gatenby
Importance: While systemic therapy for disseminated cancer is often initially successful, malignant cells, using diverse adaptive strategies encoded in the human genome, almost invariably evolve resistance, leading to treatment failure. Thus, the Darwinian dynamics of resistance are formidable barriers to all forms of systemic cancer treatment but rarely integrated into clinical trial design or included within precision oncology initiatives. Observations: We investigate cancer treatment as a game theoretic contest between the physician's therapy and the cancer cells' resistance strategies...
August 9, 2018: JAMA Oncology
David L Wilson, Andrew A Beharry, Avinash Srivastava, Timothy R O'Connor, Eric T Kool
The DNA repair enzyme ALKBH2 is implicated in both tumorigenesis as well as resistance to chemotherapy in certain cancers. It is currently under study as a potential diagnostic marker and has been proposed as a therapeutic target. To date, however, there exist no direct methods for measuring the repair activity of ALKBH2 in vitro or in biological samples. Here we report a highly specific, fluorogenic probe design based on an oligonucleotide scaffold that reports directly on ALKBH2 activity both in vitro and in cell lysates...
August 11, 2018: Angewandte Chemie
Minhong Shen, Yibin Kang
Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing...
August 10, 2018: Frontiers of Medicine
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