Drug Resistance Updates RSS feed: Articles in Press. Drug Resistance Updates is a bimonthly publication that contains thought-provoking reviews and commentaries on important developments in drug resistance in infectious disease and cancer. It covers both basic research and clinical aspects of drug resistance, and involves disciplines as diverse as molecular biology, biochemistry, cell biology, pharmacology, microbiology, oncology and clinical medicine. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. • Reviews the best in clinical and basic drug resistance research in oncology and infectious disease • Describes emerging technologies and therapies • Highlights key references in the drug resistance literature • Features commentaries on important research articles • Emphasises common themes in microbial and cancer research Features include: • Clear, concise reviews • Interdisciplinary perspectives • Summary tables and figures to convey key points • Conference reports • Literature analysis If you have a suggestion for a review article title or wish to discuss the opportunity to publish a manuscript of your own in Drug Resistance Updates , please contact the the Publisher: andrew.miller@elsevier.com .http://www.drupjournal.com//inpress?rss=yesElsevier Inc.en © 2010 Elsevier Ltd. All rights reserved. Drug Resistance Updates1368-76462010-08-27 © 2010 Elsevier Ltd. All rights reserved. healthpermissions@elsevier.comhttp://www.drupjournal.com/article/PIIS1368764610000361/abstract?rss=yesAbstract: The ability to prospectively isolate breast cancer cells that initiate tumors when transplanted orthotopically into immunocompromised mice has led to an explosion of work characterizing these cells and establishing ways to target them. Microarray studies screening for novel targets and chemical library screens for effective therapies have implicated signaling pathways, tumor–stromal interactions, miRNAs and possible even piwi-interacting (piRNAs) in the regulation of tumor initiating cell self-renewal. Potential targeting agents including the β-catenin inhibitor sulforaphane, AKT inhibitor perfosine, hedgehog inhibitor cyclopamine, stromal interaction inhibitor repertaxin, multidrug resistance pump poison dofequifar fumarate, as well as targeted the dual epidermal growth factor family inhibitor lapatinib and many more have all been found to have toxicity against purportedly chemotherapy resistant subpopulations of cancer cells often referred to as tumor initiating cells (TICs). Work using clinical samples is emerging and supports the hypothesis that neoadjuvant chemotherapy can enrich for TICs in residual disease, but strong correlation with long-term outcome is yet to be established. This paper reviews current attempts to targeting TICs and discusses the competing hypotheses to explain breast cancer recurrence and therapy resistance.The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches - Corrected ProofLara Lacerda, Lajos Pusztai, Wendy A. Woodward10.1016/j.drup.2010.08.001Drug Resistance Updates (2010)2010-08-27Drug Resistance Updates2010-08-27http://www.drupjournal.com/article/PIIS136876461000035X/abstract?rss=yesAbstract: Although chemotherapy is an important therapeutic strategy for cancer treatment, it fails to eliminate all tumor cells due to intrinsic or acquired drug resistance, which is the most common cause of tumor recurrence. Emerging evidence suggests an intricate role of cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT)-type cells in anticancer drug resistance. Recent studies also demonstrated that microRNAs (miRNAs) play critical roles in the regulation of drug resistance. Here we will discuss current knowledge regarding CSCs, EMT and the role of regulation by miRNAs in the context of drug resistance, tumor recurrence and metastasis. A better understanding of the molecular intricacies of drug-resistant cells will help to design novel therapeutic strategies by selective targeting of CSCs and EMT-phenotypic cells through alterations in the expression of specific miRNAs towards eradicating tumor recurrence and metastasis. A particular promising lead is the potential synergistic combination of natural compounds that affect critical miRNAs, such as curcumin or epigallocatechin-3-gallate (EGCG) with chemotherapeutic agents.Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistance - Corrected ProofZhiwei Wang, Yiwei Li, Aamir Ahmad, Asfar S. Azmi, Dejuan Kong, Sanjeev Banerjee, Fazlul H. Sarkar10.1016/j.drup.2010.07.001Drug Resistance Updates (2010)2010-08-09Drug Resistance Updates2010-08-09http://www.drupjournal.com/article/PIIS1368764610000348/abstract?rss=yesAbstract: The cellular transcription factor E2F1 has been identified as a tumor suppressor regulating the activities of p53 and its homologue TAp73, and promoting apoptosis by the activation of a plethora of death pathways. More than 15 years of experimentation recognized E2F1 as the key player in apoptosis induced by DNA damage in all types of human cancer. This occurs by several mechanisms that affect RB-E2F1 interaction, E2F1 stability and its binding to promoters of E2F1-regulated genes. Recent progress has been made in revealing new proapoptotic genes regulated by E2F1 and it seems that many still remain to be discovered. However, whereas in the past one focused mainly on identifying E2F1 target genes translating cellular stress signals into cell death, today the DNA damage-induced regulatory network governing E2F1's ability to induce apoptosis is rapidly gaining attention as well. Notably, the lately uncovered role of pRB and E2F3 in triggering E2F1-dependent apoptosis through chemotherapy gains our understanding of the DNA damage response in normal and tumor cells. In this context a large body of evidence indicates that nuclear cofactors targeting E2F1 seem to have a major impact on its tumor suppressor function. These new findings are discussed in the context of preclinical studies applying E2F1 overexpression in combination with genotoxic anticancer agents – called chemogene therapy, thereby providing new mechanistic links between the E2F1-induced apoptotic programming and advanced cancer phenotype.Translating DNA damage into cancer cell death—A roadmap for E2F1 apoptotic signalling and opportunities for new drug combinations to overcome chemoresistance - Corrected ProofDavid Engelmann, Brigitte M. Pützer10.1016/j.drup.2010.06.001Drug Resistance Updates (2010)2010-08-02Drug Resistance Updates2010-08-02http://www.drupjournal.com/article/PIIS1368764610000312/abstract?rss=yesAbstract: Polymyxins act by binding to lipid A moiety of the bacterial lipopolysaccharide and subsequently disintegrating the bacterial membranes. The most important mechanism of resistance includes modifications of the bacterial outer membrane structure, including lipopolysaccharide. Lipopolysaccharide modification is mostly mediated by PmrA/PmrB and PhoP/PhoQ two-component regulatory systems. These mechanisms exist with some differences in many gram-negative bacterial species. Resistance to polymyxins is generally less than 10%. In specific regions, such as the Mediterranean basin, Korea and Singapore, they tend to be higher. Heteroresistance to polymyxins is associated with exposure to polymyxins and especially suboptimal therapeutic dosage. Polymyxin combination regimens, tigecycline and fosfomycin may be useful options for the treatment of polymyxin-resistant gram-negative infections.Resistance to polymyxins: Mechanisms, frequency and treatment options - Corrected ProofMatthew E. Falagas, Petros I. Rafailidis, Dimitrios K. Matthaiou10.1016/j.drup.2010.05.002Drug Resistance Updates (2010)2010-06-18Drug Resistance Updates2010-06-18http://www.drupjournal.com/article/PIIS136876461000021X/abstract?rss=yesAbstract: Strand-transfer inhibitors, of which raltegravir, elvitegravir and S/GSK1349572, is a new class of antiretrovirals that inhibit HIV integrase-catalyzed insertion of the HIV-1 genome into cell chromosomes. The results of clinical trials were very encouraging regarding their viral efficiency and tolerance. However resistance mutations were identified in patients failing to respond to treatment with these inhibitors, involving primary mutations as well as numerous secondary mutations. This review focuses on recent advanced computational studies that have highlighted the contribution of those residues subject to primary mutations and the role of conformational flexibility of the enzyme in binding to strand-transfer inhibitors.Resistance to HIV-1 integrase inhibitors: A structural perspective - Corrected ProofJean-François Mouscadet, Olivier Delelis, Anne-Geneviève Marcelin, Luba Tchertanov10.1016/j.drup.2010.05.001Drug Resistance Updates (2010)2010-06-07Drug Resistance Updates2010-06-07