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Articles Related to Drug resistance

Mechanisms of Resistance to Kinase Inhibitors and Strategies to Prevent the Development of Drug Resistance

Targeting mutant proteins and associated signaling pathways of driver oncogenes by small molecule kinase inhibitors (KIs) are a promising strategy of cancer therapy. However, despite the initial success of treatment, KIs often become ineffective as intrinsic and acquired resistance. This article reviews the English-language literature to explore the underlying mechanisms of drug resistance and to present a challenge for developing drugs to overcome resistance. Mechanisms of acquired resistance include 1) the selection of pre-existing subclones with other mutations, 2) the emergence of secondary mutations in the target kinase domain, 3) upregulation of kinases both within the same kinase family and their related kinase families, as well as activation of alternative bypass pathways, 4) epithelial-mesenchymal transition, 5) overexpression of pro-survival Bcl-2 family proteins and 6) drug efflux mechanisms. Currently available methods are to obtain tumor biopsy samples at recurrence or progression if the tumor lesion is accessible to a biopsy and to use the second- and third-generation KIs based on the individual need of each patient. Furthermore, recent computational challenges provide design principles to prevent the development of drug resistance. In conclusion, we provide an overview of the postulated resistance mechanisms and highlight the future direction of computational structure-based design of new potent KIs.
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HIV-1 Molecular Characterization and Transmitted Drug Resistance Prevalence among Treatment-Naïve Individuals

The distribution of different human immunodeficiency virus type 1 (HIV-1) genotypes and the prevalence of transmitted drug resistance (TDR) mutations vary greatly across different Brazilian regions. This study aimed to describe the HIV-1 molecular diversity and TDR prevalence among treatment-naïve HIV-1 infected individuals in an urban area of Northeastern Brazil. DNA samples from 97 infected individuals were obtained and pol sequences were generated by Polimerase Chain Reaction (PCR) and direct sequencing. Bioinformatics tools were used to identify the presence of associated mutations with drug resistance, to reconstruct the phylogeny and to detect recombination.
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Increased High Mobility Group Protein A2/SMAD3 Relates to Ovarian Cancer Progression

The high mortality associated with ovarian cancer is generally related to the development of drug-resistant disease. HMGA2 protein, a member of the high-mobility group AT-hook (HMGA) family of non-histone chromatin binding factors, is overexpressed in high-grade serous ovarian and tubal carcinomas, though little is known about its contribution to disease progression and drug resistance. We sought to assess whether compositional changes in HMGA2 production were associated with ovarian cancer progression.
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Editorial Board Members Related to Drug resistance

Asma Amleh

Assistant Professor
Department of Biology
American University in Cairo
Egypt

Jayasimha Rao

Associate Professor
Jefferson College of Health Sciences
Department of Medicine
USA

Yanyan Li

Assistant Professor
Department of Health and Nutrition Sciences
Montclair State University
United States

HONGWEI HOLLY YIN

Assistant Professor
Cancer and Cell Biology Division
Translational Genomics Research Institute
United States

AMY H. TANG

Associate Professor
Department of Microbiology and Molecular Cell Biology
Eastern Virginia Medical School
United States

PREET M. CHAUDHARY

Professor
Department of Medicine
University of Southern California
United States

Xiaoyan Jiang

Professor
Department of Medical Genetics
University of British Colombia
Canada

Baolin Zhang

Division of Therapeutic Proteins
Office of Biotechnology Products
FDA/Center for Drug Evaluation and Research
United States

Dong-Hua Yang

Assistant Professor
Fox Chase Cancer Center
United States

Steve A. Maxwell

Associate Professor
Department of Molecular and Cellular Medicine
Texas A&M Health Science Center
United States
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