2,229 results found
    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. Cell Biology
    2. Computational and Systems Biology

    Perturbation biology nominates upstream–downstream drug combinations in RAF inhibitor resistant melanoma cells

    Anil Korkut et al.
    Data-driven systems biology models of signaling predict cellular response to untested perturbations and can nominate drug combinations to overcome drug resistance in cancer cells.
    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. Cancer Biology
    2. Cell Biology

    Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2

    Qian Liu et al.
    The pro-apoptotic BH3-protein Bim contains two distinct binding sites for anti-apoptotic proteins that together confer resistance of Bim/Bcl-2 and Bim/Bcl-XL complexes to BH3-mimetic drugs under development for use in humans.
    1. Cancer Biology

    NFATc2 enhances tumor-initiating phenotypes through the NFATc2/SOX2/ALDH axis in lung adenocarcinoma

    Zhi-Jie Xiao et al.
    NFATc2 maintains the drug-induced TIC phenotypes through trans-activating SOX2/ALDH1A1 expression and scavenging stress from ROS.
    1. Cancer Biology

    Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers

    Ganesh V Raj et al.
    A novel first-in-class small molecule (ERX-11) that interacts with and disrupts the interactome of the estrogen receptor (ER), blocks the growth of ER-positive breast cancers, including those that are resistant to currently approved hormonal agents.
    1. Cancer Biology

    Inhibition of mutant EGFR in lung cancer cells triggers SOX2-FOXO6-dependent survival pathways

    S Michael Rothenberg et al.
    SOX2 causes resistance to anti-EGFR therapies in EGFR-mutant lung cancer.
    1. Cancer Biology
    2. Developmental Biology

    Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening

    Carla S Verissimo et al.
    Libraries of patient-derived tumor organoids are a reliable and scalable model system that can help identify and optimize targeted therapies in a pre-clinical setting.
    1. Cell Biology

    Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits

    Diego Acosta-Alvear et al.
    The nodes of the cytosolic proteostasis network can control sensitivity to proteasome inhibitors and decreased levels of the 19S proteasomal regulator can lead to increased resistance to inhibitors.
    1. Cancer Biology
    2. Cell Biology

    The CUL5 ubiquitin ligase complex mediates resistance to CDK9 and MCL1 inhibitors in lung cancer cells

    Shaheen Kabir et al.
    Targeting the CRL5 ubiquitin ligase complex in combination with CDK9 or MCL1 inhibition could combat innate and acquired resistance of cancer cells to MCL1-targeting therapeutics.

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