ArticleBiomaterials2015
Deconstructing the role of the ECM microenvironment on drug efficacy targeting MAPK signaling in a pre-clinical platform for cutaneous melanoma.
Article in Biomaterials, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- YAP localization mediates mechanical adaptation of human cancer cells during extravasationbioRxiv : the preprint server for biology · 2023Article
- The impact of microfluidics in high-throughput drug-screening applications.Biomicrofluidics · 2022Review
- 3D Cell Culture for the Study of Microenvironment-Mediated Mechanostimuli to the Cell Nucleus: An Important Step for Cancer Research.Frontiers in molecular biosciences · 2021Article
- ADAMTS-15 Has a Tumor Suppressor Role in Prostate Cancer.Biomolecules · 2020Article
- A novel ex vivo tumor system identifies Src-mediated invasion and metastasis in mesenchymal tumor cells in non-small cell lung cancer.Scientific reports · 2019Article
- Intersection of Brain Development and Paediatric Diffuse Midline Gliomas: Potential Role of Microenvironment in Tumour Growth.Brain sciences · 2018Review
- Perspective: The role of mechanobiology in the etiology of brain metastasis.APL bioengineering · 2018Article
- Engineering and physical sciences in oncology: challenges and opportunities.Nature reviews. Cancer · 2017Review
- Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models.Stem cell reviews and reports · 2017Review
- Heralding a new paradigm in 3D tumor modeling.Biomaterials · 2016Review
- Stimulatory effects of the degradation products from Mg-Ca-Sr alloy on the osteogenesis through regulating ERK signaling pathway.Scientific reports · 2016Article
- Article
- In vivo tissue has non-linear rheological behavior distinct from 3D biomimetic hydrogels, as determined by AMOTIV microscopy.Biomaterials · 2016Article
- Recapitulating the Tumor Ecosystem Along the Metastatic Cascade Using 3D Culture Models.Frontiers in oncology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Therapeutics targeting the BRAF kinase in cutaneous melanoma have significantly improved patient survival. However, durable responses in the face of metastatic disease are rarely realized where the problem of brain metastases is generally growing in magnitude. Tumor and stromal cells dynamically remodel the extracellular matrix (ECM) during the establishment of a metastatic lesion. We reasoned that ECM composition strongly determines drug efficacy on cell motility, adhesion and viability rendering one drug more potent and another less so. To test this hypothesis, we constructed platforms recreating the ECM composition due to the stroma and tumor cells, mimicking the brain's perivascular niche and hyaluronic acid (HA) rich parenchyma. Using human melanoma cell lines, we observed that cell adhesion was minimally affected by BRAF inhibition but ablated by ERK inhibition. Cell motility was impaired for both drugs. We determined that the composition and architecture of the ECM niche modulated drug efficacy. In one series, potency of BRAF inhibition was blunted in 3D Fibronectin-HA hydrogels whereas Laminin-HA hydrogels protected against ERK inhibition. In the other series, Laminin blunted drug efficacy, despite both series sharing the same BRAF mutation. These data reinforce the importance of contextual drug assessment in designing future therapeutics.
Indexed as
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.