Drug Resistance Updates RSS feed: Current Issue. 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/?rss=yesElsevier Inc.en © 2011 Published by Elsevier Inc. All rights reserved. Drug Resistance Updates1368-7646146December 2011 © 2011 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.drupjournal.com/article/PIIS1368764611000653/abstract?rss=yesEditorial Board10.1016/S1368-7646(11)00065-3Drug Resistance Updates 14, 6 (2011)2011-12-01Drug Resistance Updates2011-12-01146S1368-7646(11)X0006-7iihttp://www.drupjournal.com/article/PIIS1368764611000628/abstract?rss=yesHighlights: ► Although acyclovir and related compounds are effective herpes simplex virus therapies, drug resistance is an important clinical problem. ► Frameshift mutations in the viral thymidine kinase gene, which encodes the enzyme that activates acyclovir, are frequently observed in drug-resistant viruses. ► The frameshift mutations may be associated with low levels of thymidine kinase expression; too low to activate drug but sufficient to support pathogenesis. ► Mechanisms exploited to compensate for frameshift mutations include ribosomal frameshifting, internal ribosome entry, and induced infidelity of the DNA polymerase.Abstract: Some of the most successful antiviral agents currently available are effective against herpes simplex virus. However, resistance to these drugs is frequently associated with significant morbidity, particularly in immunocompromised patients. In addition to the clinical implications of drug resistance, the range of biological processes exploited by the virus to attain resistance while maintaining pathogenicity is proving to be surprising. These mechanisms, which include ribosomal frameshifting, induced infidelity of the DNA polymerase, and internal ribosome entry, are discussed.Slipping and sliding: Frameshift mutations in herpes simplex virus thymidine kinase and drug-resistanceAnthony Griffiths10.1016/j.drup.2011.08.003Drug Resistance Updates 14, 6 (2011)2011-09-23Drug Resistance Updates2011-09-23146S1368-7646(11)X0006-7251259http://www.drupjournal.com/article/PIIS1368764611000616/abstract?rss=yesHighlights: ► Although inhibition of EGFR and other ERBB-family proteins is a standard approach in cancer, diverse resistance mechanisms limit efficacy of this strategy. ► We summarize current and developing small molecule and antibody tools for inhibiting EGFR and cooperating proteins, describe sources of intrinsic and acquired resistance to these inhibitors, and discuss future trends for integration of EGFR/ERBB-targeting agents with other therapies.Abstract: Agents targeting EGFR and related ErbB family proteins are valuable therapies for the treatment of many cancers. For some tumor types, including squamous cell carcinomas of the head and neck (SCCHN), antibodies targeting EGFR were the first protein-directed agents to show clinical benefit, and remain a standard component of clinical strategies for management of the disease. Nevertheless, many patients display either intrinsic or acquired resistance to these drugs; hence, major research goals are to better understand the underlying causes of resistance, and to develop new therapeutic strategies that boost the impact of EGFR/ErbB inhibitors. In this review, we first summarize current standard use of EGFR inhibitors in the context of SCCHN, and described new agents targeting EGFR currently moving through pre-clinical and clinical development. We then discuss how changes in other transmembrane receptors, including IGF1R, c-Met, and TGF-β, can confer resistance to EGFR-targeted inhibitors, and discuss new agents targeting these proteins. Moving downstream, we discuss critical EGFR-dependent effectors, including PLC-γ; PI3K and PTEN; SHC, GRB2, and RAS and the STAT proteins, as factors in resistance to EGFR-directed inhibitors and as alternative targets of therapeutic inhibition. We summarize alternative sources of resistance among cellular changes that target EGFR itself, through regulation of ligand availability, post-translational modification of EGFR, availability of EGFR partners for hetero-dimerization and control of EGFR intracellular trafficking for recycling versus degradation. Finally, we discuss new strategies to identify effective therapeutic combinations involving EGFR-targeted inhibitors, in the context of new system level data becoming available for analysis of individual tumors.Protein-intrinsic and signaling network-based sources of resistance to EGFR- and ErbB family-targeted therapies in head and neck cancerRanee Mehra, Ilya G. Serebriiskii, Roland L. Dunbrack, Matthew K. Robinson, Barbara Burtness, Erica A. Golemis10.1016/j.drup.2011.08.002Drug Resistance Updates 14, 6 (2011)2011-09-19Drug Resistance Updates2011-09-19146S1368-7646(11)X0006-7260279http://www.drupjournal.com/article/PIIS1368764611000604/abstract?rss=yesHighlights: ► Colorectal cancer (CRC) is the second cause of cancer-related deaths in the world. ► Despite therapeutic advancements, CRC drug resistance is the main cause of treatment failure. ► Epigenetics may play a key role in chemoresistance. ► Epigenetic mechanisms of resistance to 5-FU, irinotecan and oxaliplatin in CRC are described. ► Drug resistance modulation by epigenetic drugs may contribute to improve therapeutic outcome.Abstract: Colorectal cancer is the second leading cause of cancer-related deaths in the world. Despite many therapeutic opportunities, prognosis remains dismal for patients with metastatic disease, and a significant portion of early-stage patients develop recurrence after chemotherapy. Epigenetic gene regulation is a major mechanism of cancer initiation and progression, through the inactivation of several tumor suppressor genes. Emerging evidence indicates that epigenetics may also play a key role in the development of chemoresistance. In the present review, we summarize epigenetic mechanisms triggering resistance to three commonly used agents in colorectal cancer: 5-fluorouracil, irinotecan and oxaliplatin. Those epigenetic biomarkers may help stratify colorectal cancer patients and develop a tailored therapeutic approach. In addition, epigenetic modifications are reversible through specific drugs: histone-deacetylase and DNA-methyl-transferase inhibitors. Preclinical studies suggest that these drugs may reverse chemoresistance in colorectal tumors. In conclusion, an epigenetic approach to colorectal cancer chemoresistance may pave the way to personalized treatment and to innovative therapeutic strategies.Epigenetics and chemoresistance in colorectal cancer: An opportunity for treatment tailoring and novel therapeutic strategiesFrancesco Crea, Stefania Nobili, Elisa Paolicchi, Gabriele Perrone, Cristina Napoli, Ida Landini, Romano Danesi, Enrico Mini10.1016/j.drup.2011.08.001Drug Resistance Updates 14, 6 (2011)2011-09-28Drug Resistance Updates2011-09-28146S1368-7646(11)X0006-7280296