Biofilms as a mechanism of bacterial resistance
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Anne Jolivet-Gougeon , Martine Bonnaure-Mallet Inside the biofilm, antimicrobial agents must overcome high cell density, an increased number of resistant mutants, substance delivery, molecular exchanges, such as high levels of beta-lactamases or inducers of efflux pump expression, and specific adaptive cells, so-called persisters. The environment within the biofilm modulates the response to antibiotics, especially when the SOS response or DNA repair systems are involved. Exposure to subinhibitory concentrations of antibiotics...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
The role of the microenvironment-dormant prostate disseminated tumor cells in the bone marrow
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Hung-Ming Lam , Robert L. Vessella , Colm Morrissey Disseminated tumor cells (DTC) leave the primary tumor and reside in distant sites (e.g. bone) early in prostate cancer. Patients may harbor dormant DTC which develop into clinically overt metastasis years after radical prostatectomy. We will describe recent evidence suggesting high p38/ERK ratio, bone morphogenetic proteins, and tumor growth factor-beta 2 promote dormancy in solid tumors. Furthermore, we will discuss the possible regulation of dormancy by hematopoietic ste...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
General principles of antibiotic resistance in bacteria
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Jose L. Martinez Given the impact of antibiotic resistance on human health, its study is of great interest from a clinical viewpoint. In addition, antibiotic resistance is one of the few examples of evolution that can be studied in real time. Knowing the general principles involved in the acquisition of antibiotic resistance is therefore of interest to clinicians, evolutionary biologists and ecologists. The origin of antibiotic resistance genes now possessed by human pathogens can be traced back to environmental microorganisms...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Resistance to Raf inhibition in cancer
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): H. Eirik Haarberg , Keiran S.M. Smalley The use of small molecule BRAF inhibitors has revolutionized the treatment of advanced melanoma. Despite this, resistance is commonplace and associated with a median progression-free survival of >5 months. Major resistance mechanisms include reactivation of the MAPK pathway and increased PI3K/AKT signaling. Here we review some of the combination therapeutic strategies currently undergoing evaluation for the management of acquired drug resistance in melanoma. (Source: Drug Discove...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Genetic barrier and variant fitness in hepatitis C as critical parameters for drug resistance development
This article illustrates the basic mechanisms underlying development of resistance to specific antiviral agents with a special emphasis on NS3 protease inhibitors. The role of fitness deficits and compensation for variant selection and persistence is discussed together with technical issues in sequencing as well as clinical implications in the use of DAAs now and in the future. (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Use of RNAi screens to uncover resistance mechanisms in cancer cells and identify synthetic lethal interactions
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Paul Diehl , Donato Tedesco , Alex Chenchik RNAi loss-of-function screens, which have proven effective to identify genes functionally responsible for cellular phenotypes, can be designed to use different genetic backgrounds or altered environmental conditions to elucidate genetic dependencies. These sorts of screening approaches can be exploited to identify genetic targets that minimize resistance to approved drugs, and provide a basis on which to develop new targeted therapies and predict the secondary targets for combinato...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
New resistance mechanisms for small molecule kinase inhibitors of Abl kinase
Publication date: March 2014 Source:Drug Discovery Today: Technologies, Volume 11 Author(s): Michele Modugno Mutations in the kinase domain of Bcr-Abl are the most common cause of resistance to therapy with Imatinib in patients with chronic myelogenous leukaemia (CML). Second generation Bcr-Abl inhibitors, such as Nilotinib and Dasatinib, are able to overcome most Imatinib-resistant mutants, with the exception of the T315I substitution. Structural studies of Abl wild-type and T315I mutant have provided better understanding of how this mutation leads to resistance and have been used to support the drug design process f...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
