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    1. Cancer Biology
    2. Computational and Systems Biology

    A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity

    Adam C Palmer et al.
    Drugs in a curative chemotherapy regimen are independently effective and resisted by different mechanisms, so cancer cells have little chance of surviving all drugs, and this benefit occurs without synergistic interactions.
    1. Cancer Biology

    Overcoming mutation-based resistance to antiandrogens with rational drug design

    Minna D Balbas et al.
    Mutagenesis studies identified an androgen receptor mutation that converts enzalutamide-a drug recently approved for the treatment of advanced prostate cancer-into an androgen receptor agonist, and modeling studies informed the design of novel drugs that are effective against the mutant receptor.
    1. Evolutionary Biology
    2. Physics of Living Systems

    Price equation captures the role of drug interactions and collateral effects in the evolution of multidrug resistance

    Erida Gjini, Kevin B Wood
    A simple mathematical model reveals that antibiotic interactions and collateral effects of evolution are inseparable drivers of multidrug resistance linked by the well-known Price equation from evolutionary theory.
    1. Cancer Biology

    SATB2 induction of a neural crest mesenchyme-like program drives melanoma invasion and drug resistance

    Maurizio Fazio et al.
    A genetic discovery screen for epigenetic factors accelerating melanoma development in vivo identifies SATB2 as a driver of tumor invasion and resistance to FDA-approved BRAF-targeted inhibitor Vemurafenib.
    1. Microbiology and Infectious Disease

    Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure

    Fernando J Sánchez-Valdéz et al.
    Intracellular amastigotes of the Chagas disease agent Trypanosoma cruzi can spontaneously enter an extended state of replicative dormancy, during which time they are resistant to drug treatment both in vitro and in vivo.
    1. Evolutionary Biology

    Rapid decline of bacterial drug-resistance in an antibiotic-free environment through phenotypic reversion

    Anett Dunai et al.
    Drug-resistance declines in the laboratory in an antibiotic stress-free environment, indicating that restricting antimicrobial usage in the clinics could be a useful policy.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Genome plasticity in Candida albicans is driven by long repeat sequences

    Robert T Todd et al.
    Previously uncharacterized long repeat sequences are associated with significant genome variation that can increase fitness and promote antifungal drug resistance in diverse isolates of Candida albicans.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance

    Luana C Mathieu et al.
    The de novo selection of a mutation responsible for Plasmodium falciparum in vitro artemisinin resistance is confirmed in Guyana, making artemisinin combination therapies vulnerable to complete resistance in this region.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei

    Ali H Alghamdi et al.
    Study of TbAQP2 adaptations and substrate interactions shows how this aquaglyceroporin enables cellular entry of large antimicrobial agents in Trypanosoma brucei.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    Structural basis for potent and broad inhibition of HIV-1 RT by thiophene[3,2-d]pyrimidine non-nucleoside inhibitors

    Yang Yang et al.
    High-resolution structures of HIV-1 RT in complex with two newly developed non-nucleoside inhibitors explain how they retain antiviral activities against drug-resistant RT mutants with considerably reduced susceptibility to rilpivirine.