ArticleCancers2020
Mutant Kras as a Biomarker Plays a Favorable Role in FL118-Induced Apoptosis, Reactive Oxygen Species (ROS) Production and Modulation of Survivin, Mcl-1 and XIAP in Human Bladder Cancer.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Pseudolaric acid B promotes lung cancer cells ferroptosis depending on JNK/ERK-mediated upregulation of survivin.Scientific reports · 2026Article
- Growth Hormone Signaling in Bladder Cancer: Transcriptomic Profiling of Patient Samples and In Vitro Evidence of Therapy Resistance via ABC Transporters and EMT Activation.International journal of molecular sciences · 2025Article
- Design, synthesis and investigation of biological activity and mechanism of fluoroaryl-substituted derivatives at the FL118 position 7.European journal of medicinal chemistry · 2025Article
- Dibenzolium induces apoptosis and inhibits epithelial-mesenchymal transition (EMT) in bladder cancer cell lines.Scientific reports · 2024Article
- Structure-Activity Relationship of FL118 Platform Position 7 Versus Position 9-Derived Compounds and Their Mechanism of Action and Antitumor Activity.Journal of medicinal chemistry · 2023Article
- High-quality and robust protein quantification in large clinical/pharmaceutical cohorts with IonStar proteomics investigation.Nature protocols · 2023Review
- Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma.Biomarker research · 2023Review
- FL118, acting as a 'molecular glue degrader', binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy.Clinical and translational medicine · 2022Article
- Article
- Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- CircCA12 Promotes Malignant Process via Sponging miR-1184 and Upregulating RAS Family in Bladder Cancer.Frontiers in genetics · 2021Article
- Long Non-Coding RNAs as Biomarkers and Therapeutic Targets in Sepsis.Frontiers in immunology · 2021Review
- Kras mutation subtypes distinctly affect colorectal cancer cell sensitivity to FL118, a novel inhibitor of survivin, Mcl-1, XIAP, cIAP2 and MdmX.American journal of translational research · 2021Article
- Multiple functions of the DEAD-box RNA helicase, DDX5 (p68), make DDX5 a superior oncogenic biomarker and target for targeted cancer therapy.American journal of cancer research · 2021Review
- Molecular Characterization of the Clinical and Tumor Immune Microenvironment Signature of 5-methylcytosine-Related Regulators in non-small Cell Lung Cancer.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumor heterogeneity in key gene mutations in bladder cancer (BC) is a major hurdle for the development of effective treatments. Using molecular, cellular, proteomics and animal models, we demonstrated that FL118, an innovative small molecule, is highly effective at killing T24 and UMUC3 high-grade BC cells, which have Hras and Kras mutations, respectively. In contrast, HT1376 BC cells with wild-type Ras are insensitive to FL118. This concept was further demonstrated in additional BC and colorectal cancer cells with mutant Kras versus those with wild-type Kras. FL118 strongly induced PARP cleavage (apoptosis hallmark) and inhibited survivin, XIAP and/or Mcl-1 in both T24 and UMUC3 cells, but not in the HT1376 cells. Silencing mutant Kras reduced both FL118-induced PARP cleavage and downregulation of survivin, XIAP and Mcl-1 in UMUC3 cells, suggesting mutant Kras is required for FL118 to exhibit higher anticancer efficacy. FL118 increased reactive oxygen species (ROS) production in T24 and UMUC3 cells, but not in HT1376 cells. Silencing mutant Kras in UMUC3 cells reduced FL118-mediated ROS generation. Proteomics analysis revealed that a profound and opposing Kras-relevant signaling protein is changed in UMUC3 cells and not in HT1376 cells. Consistently, in vivo studies indicated that UMUC3 tumors are highly sensitive to FL118 treatment, while HT1376 tumors are highly resistant to this agent. Silencing mutant Kras in UMUC3 cell-derived tumors decreases UMUC3 tumor sensitivity to FL118 treatment. Together, our studies revealed that mutant Kras is a favorable biomarker for FL118 targeted treatment.
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