ArticleBritish journal of cancer2013
Acute tumour response to the MEK1/2 inhibitor selumetinib (AZD6244, ARRY-142886) evaluated by non-invasive diffusion-weighted MRI.
Article in British journal of cancer, 2013. 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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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Ex Vivo MR Histology and Cytometric Feature Mapping Connect Three-dimensional in Vivo MR Images to Two-dimensional Histopathologic Images of Murine Sarcomas.Radiology. Imaging cancer · 2021Article
- Theranostics Targeting Fibroblast Activation Protein in the Tumor Stroma:Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Article
- Decoding Melanoma Development and Progression: Identification of Therapeutic Vulnerabilities.Frontiers in oncology · 2020Review
- Article
- Imaging markers of response to combined BRAF and MEK inhibition in BRAF mutated vemurafenib-sensitive and resistant melanomas.Oncotarget · 2018Article
- Article
- Current Development Status of MEK Inhibitors.Molecules (Basel, Switzerland) · 2017Review
- Detecting human melanoma cell re-differentiation following BRAF or heat shock protein 90 inhibition using photoacoustic and magnetic resonance imaging.Scientific reports · 2017Article
- Use of non-invasive imaging to monitor response to aflibercept treatment in murine models of colorectal cancer liver metastases.Clinical & experimental metastasis · 2017Article
- Review
- The Synergistic Effect of Selumetinib/Docetaxel Combination Therapy Monitored by [(18)F]FDG/[(18)F]FLT PET and Diffusion-Weighted Magnetic Resonance Imaging in a Colorectal Tumor Xenograft Model.Molecular imaging and biology · 2016Article
- Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts.Oncotarget · 2015Article
- Diffusion-weighted MRI for imaging cell death after cytotoxic or apoptosis-inducing therapy.British journal of cancer · 2015Article
- Acquired resistance to EGFR tyrosine kinase inhibitors alters the metabolism of human head and neck squamous carcinoma cells and xenograft tumours.British journal of cancer · 2015Article
- MRI reveals the in vivo cellular and vascular response to BEZ235 in ovarian cancer xenografts with different PI3-kinase pathway activity.British journal of cancer · 2015Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundNon-invasive imaging biomarkers underpin the development of molecularly targeted anti-cancer drugs. This study evaluates tumour apparent diffusion coefficient (ADC), measured by diffusion-weighted magnetic resonance imaging (DW-MRI), as a biomarker of response to the MEK1/2 inhibitor selumetinib (AZD6244, ARRY-142886) in human tumour xenografts.
methodsNude mice bearing human BRAF(V600D) WM266.4 melanoma or BRAF(V600E) Colo205 colon carcinoma xenografts were treated for 4 days with vehicle or selumetinib. DW-MRI was performed before and 2 h after the last dose and excised tumours analysed for levels of phospho-ERK1/2, cleaved caspase 3 (CC3) and necrosis.
resultsSelumetinib treatment induced tumour stasis and reduced ERK1/2 phosphorylation in both WM266.4 and Colo205 tumour xenografts. Relative to day 0, mean tumour ADC was unchanged in the control groups but was significantly increased by up to 1.6-fold in selumetinib-treated WM266.4 and Colo205 tumours. Histological analysis revealed a significant increase in necrosis in selumetinib-treated WM266.4 and Colo205 xenografts and CC3 staining in selumetinib-treated Colo205 tumours relative to controls.
conclusionChanges in ADC following treatment with the MEK1/2 inhibitor selumetinib in responsive human tumour xenografts were concomitant with induction of tumour cell death. ADC may provide a useful non-invasive pharmacodynamic biomarker for early clinical assessment of response to selumetinib and other MEK-ERK1/2 signalling-targeted therapies.
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