ArticleScience advances2022
Overcoming differential tumor penetration of BRAF inhibitors using computationally guided combination therapy.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Therapeutic Resistance in Melanoma: Molecular Mechanisms and Emerging Pharmaceutical Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Associations of Tumor Somatic Mutations and Genetic Alterations with Survival Outcomes in Melanoma Patients Treated with Ipilimumab.Journal of clinical medicine · 2026Article
- Fluorescent PSMA-Targeted Radiotheranostic Compounds for Multiscale Imaging.Bioconjugate chemistry · 2025Article
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- Localized In Vivo Prodrug Activation Using Radionuclides.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Characterizing heterogeneous single-cell dose responses computationally and experimentally using threshold inhibition surfaces and dose-titration assays.NPJ systems biology and applications · 2024Article
- Tyrosine kinase inhibitors (TKIs) for ovarian cancer treatment: from organic to inorganic chemotherapeutics towards selectivity-a perspective overview.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma.Cancer research · 2024Article
- Chemical QuantArray: A Quantitative Tool for Mass Spectrometry Imaging.Analytical chemistry · 2023Article
- The Blood-Brain Barrier: Implications for Experimental Cancer Therapeutics.Annual review of cancer biology · 2023Article
- Dual Immunostimulatory Pathway Agonism through a Synthetic Nanocarrier Triggers Robust Anti-Tumor Immunity in Murine Glioblastoma.Advanced materials (Deerfield Beach, Fla.) · 2023Article
- Radiation Cleaved Drug-Conjugate Linkers Enable Local Payload Release.Bioconjugate chemistry · 2022Article
- Deciphering albumin-directed drug delivery by imaging.Advanced drug delivery reviews · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 6 institutions in 3 countries.
Funding
Abstract
BRAF-targeted kinase inhibitors (KIs) are used to treat malignancies including BRAF-mutant non-small cell lung cancer, colorectal cancer, anaplastic thyroid cancer, and, most prominently, melanoma. However, KI selection criteria in patients remain unclear, as are pharmacokinetic/pharmacodynamic (PK/PD) mechanisms that may limit context-dependent efficacy and differentiate related drugs. To address this issue, we imaged mouse models of BRAF-mutant cancers, fluorescent KI tracers, and unlabeled drug to calibrate in silico spatial PK/PD models. Results indicated that drug lipophilicity, plasma clearance, faster target dissociation, and, in particular, high albumin binding could limit dabrafenib action in visceral metastases compared to other KIs. This correlated with retrospective clinical observations. Computational modeling identified a timed strategy for combining dabrafenib and encorafenib to better sustain BRAF inhibition, which showed enhanced efficacy in mice. This study thus offers principles of spatial drug action that may help guide drug development, KI selection, and combination.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.